- Dr. Betty Director (voiced by Felicity Huffman) is the head of the Global Justice Network, a worldwide espionage organization. Her role and appearance are reminiscent of Marvel Comics character Nick Fury.[citation needed]
- Team Impossible are a group of operatives who initially only operate for money before Wade convinces them to join Global Justice and become non-profit. They consist of Dash (voiced by Gary Dourdan), Crash (voiced by Eric Close), and Burn (voiced by Adam Rodriguez).
- Will Du (voiced by BD Wong) is a top agent at Global Justice. He initially clashes with Kim before working with her to stop Duff Killigan.
Yamanouchi is a secret ninja school, located atop a mountain in Japan. It was founded by Toshimiru, a master of Monkey Kung Fu. He carved the school out of the mountain using a sword called the Lotus Blade. Since its creation in 338 AD, the school has guarded the blade, which can only be used by those who possess Mystical Monkey Power.
- Master Sensei (voiced by George Takei) is a martial artist and the headmaster of the Yamanouchi school. He guides Ron in mastering his Mystical Monkey Powers and becoming the Ultimate Monkey Master.
- Yori (voiced by Keiko Agena) is a ninja who is sent to guide Ron to the Yamanouchi School. Since her introduction, she has appeared as a potential love interest for Ron, piquing his romantic interest at first sight and gradually developing feelings for him.
Team Go are a sibling team who protect Go City and obtained superpowers after a multicolored comet crashed into their tree house when they were young. Shego was originally a member of the team before leaving. They are each themed after a specific color and are named after pronouns, with "go" added at the end. Hego is blue, Mego is purple, the Wego twins are red, and Shego is green.
- Hego (voiced by Christopher McDonald) is the oldest member of Team Go, who possesses superhuman strength. In his civilian identity, he is a Bueno Nacho manager.
- Mego (voiced by Jere Burns) is a member of Team Go who can shrink to the size of a doll. He possesses a large ego and is defensive of his seemingly useless power.
- The Wego twins (voiced by Fred Savage) are twin members of Team Go who can duplicate themselves.
- M.C. Honey (voiced by Sherri Shepherd) is a rapper loosely based on female rappers like Queen Latifah and MC Lyte. She gives Kim a ride in her yacht as thanks for retrieving her demo tape when it was stolen in "Hidden Talent"'. She reappears in "Rappin' Drakken" and "Trading Faces".
- Britina (voiced by Tara Strong) is a teen musician who has her own line of merchandise, including a magazine and dolls. Like most pop singers, she is fodder for tabloids and is notable for her relationships; she dated Oh Boyz singer Nicky Nick, but they have since broken up. Her name is an allusion to Britney Spears and Christina Aguilera.
- Nakasumi (voiced by Clyde Kusatsu) is an esteemed toy developer, and Miss Kyoko (voiced by Lauren Tom) is his secretary and assistant. He is the victim of theft by Drakken and Shego in "Crush", but Kim recovers what was stolen, and in return, Nakasumi gives her a ride in "A Very Possible Christmas" and So the Drama.
- Amelia (voiced by Carly Pope, later Tara Strong) is a senior who is implied to be the school's beauty queen, and presumably graduates after season two. She constantly brushes off Ron's attempts at flirting, but welcomes him into her popular circle during the episodes "All the News" and "The New Ron", and accepts money from him in "Ron Millionaire".
- Bobo the Chimpanzee is Camp Wannaweep's mascot. He is only seen in flashbacks describing Ron's unpleasant experiences at the camp.
- Doctor Cyrus Bortel (voiced by Enrico Colantoni) is a selfish inventor who developed the Moodulators and Mind Control Chips.
- Doctor Vivian Porter (voiced by Shawnee Smith) is a roboticist who created the android Oliver, among other inventions. James Possible later offers her a job at the Middleton Space Center's robotics lab.
- François (voiced by Rob Paulsen) is a French hairstylist who styles Ron's hair in "The New Ron". He later appears in "Rufus in Show", when he lends Kim and Ron his prize-winning pedigree poodle when they need to infiltrate an exclusive dog show, and in "Two to Tutor" as one of the targets of a string of heists committed by Shego and Señor Senior Junior.
- Hirotaka (voiced by Brian Tochi) is a Japanese student who appears in the episode "Exchange" as a participant in the titular exchange program.
- Ned (voiced by Eddie Deezen) is an assistant manager at Bueno Nacho.
- Elsa Cleeg (voiced by Wendie Malick) is a famous fashion critic with her own television fashion report program, which Monique is a fan of. She is an influential authority on fashion, even influencing Club Banana. She was inspired by the aesthetics of Kim's mission clothes to create the "KimStyle", which became a nationwide clothing sensation, including spin-off clothing lines "KimForHim" and one for pets.
- Oh Boyz are a boy band consisting of Robby, Nicky Nick, Ryan, and Dexter, whose fame suddenly vanished, leaving Ron as their only fan. They are on the verge of breaking up when the Señor Seniors kidnap them to fulfill Junior's dream of becoming a pop star, inadvertently restoring their popularity. The four are respectively voiced by Lance Bass, Joey Fatone, Jason Marsden, and Justin Shenkarow.
- Pain King and Steel Toe (respectively voiced by Bill Goldberg and Test) are the star wrestlers of the GWA (Global Wrestling Association), who are rivals in the ring but friends outside it. They are distinguished by their costumes, which allude to their stage names – Pain King wears a gold coronet and mask, while Steel Toe's right shoe is supposedly made of titanium.
- Wally (voiced by Rob Paulsen) is the spoiled and arrogant prince of Rodeghan. Kim was charged with protecting him from the Knights of Rodeghan in "Royal Pain" because of his ancestor's tyrannical behavior toward them. Wally runs for class president against Kim and Brick Flagg, inspiring him to convert Rodeghan into a democracy.
- Private Cleotus Dobbs (voiced by Dan Castellaneta) is a private in the Army who was charged with guarding a Neutronalizer Ray. Dr. Drakken kidnaps and switches minds with him to steal the Neutronalizer.
- Professor Acari (voiced by Maurice LaMarche) is an insectologist who invented the "roflex", a device that can enlarge insects. He is named for Acariformes, an order of mite.
- Professor Ramesh (voiced by Brian George) is an astronomer and old friend of James Possible.
- Professor Robert Chen (voiced by Gedde Watanabe) is an astronomer and old friend of James Possible and Dr. Drakken.
- Rabbi Katz (voiced by Peter Bonerz) is a rabbi who oversees Ron's bar mitzvah.
- Roachie (vocal effects provided by Frank Welker) is a cockroach who Chester Yapsby enlarged to the size of a small dog using the roflex, an invention he stole from Professor Acari. Ron befriends him despite his fear of insects.
- Tara (voiced by Tara Strong) is a cheerleader and one of Bonnie's sycophants. She has dated numerous characters, including Josh Mankey and Jason Morgan.
- Timothy North (voiced by Adam West) is a former television actor who played the role of the titular character on the TV show The Fearless Ferret. Over the years, North becomes delusional and begins to believe he is the Fearless Ferret. At a Retro-TV convention, he reunites with Rudolph Farnsworth, who played the villain White Stripe and had also become delusional. This brings the two back to reality and reunites them as friends. North's name and persona are based on West's role as Batman in the 1960s series of the same name.
- Zita Flores (voiced by Nika Futterman) is a Hispanic student at Middleton High, who works at a multiplex theater in Middleton and is usually seen in the ticket booth wearing the name tag "Annie" until hers can be made. Ron has a crush on her, and so attends every film showing to chat with her, which evidently piques her interest.
Minor characters in Kim's network whom she has helped during past missions and provide transportation to her missions. As of season four, Kim uses rides less because she has her own vehicle, but calls upon them when it is out of service.
- Baxter – In "Mind Games", he lets Kim and Ron ride two of his donkeys into the Grand Canyon in return for Kim performing an emergency delivery for his donkey Buttercup. He is voiced by Dan Castellaneta.
- Bernice – In "Naked Genius", she gives Kim a ride as thanks for saving her town from a leaking dam. She also appears in "Team Impossible", having apparently started working with jets. She is voiced by April Winchell.
- Captain Louis – In "A Very Possible Christmas", he gives Ron a ride to Dr. Drakken's base. The episode reveals that Kim saved his boat from sinking, but that Ron exacerbated the trouble, which he does not remember. He is voiced by John DiMaggio.
- Dallas – In "Attack of the Killer Bebes", he gives Kim a lift to Mount Middleton after she aids him during a car chase. He is voiced by Rob Paulsen.
- Mr. Geminini – He works for Doctor Bortle, and in "The Twin Factor" gives Kim, Ron, and her brothers a ride to Bortle's lab. He has a twin, but his brother is in prison. He is voiced by Dan Castellaneta.
- Gustavo – In "Tick-Tick-Tick", he gives Kim and Ron a ride in his plane as thanks for them saving his village from a flood, which it is hinted Ron caused.
- Heinrich – In "Crush", he gives Kim a ride after she saves his village from an avalanche that Ron accidentally caused which he still holds a grudge on him for. He reappears in "Team Impossible". He is voiced by John DiMaggio.
- Joe – A helicopter pilot who in "Queen Bebe" gives Kim and Ron a ride to the Bebe's hive island off the Gulf Coast of Florida.
- Judd – A camera man who in "Oh Boyz" gives Kim a ride to the Seniors' island. Kim had rescued Judd from a rhino stampede while he was filming a program entitled "Teasing Wild Animals".
- Mr. Magnifico – In "Bonding", he and his circus company give Kim a ride to a top-secret research facility on their train. They did this in return for Kim acting as a substitute acrobat after the original performer twisted her ankle.
- Mr. Morrow - He is voiced by Clancy Brown.
- Mrs. Mahoney – A woman who gave Kim her first ever ride as payment for saving her cat, as seen in A Sitch in Time.
- Mr. Parker – In "Bueno Nacho", he flies Kim to Wisconsin in his crop duster after she saves his business by going organic, allowing her to para-drop onto the world's largest Swiss cheese wheel.
- Ricardo – In "Gorilla Fist", he gives Kim a ride to South America in his plane as thanks for saving his chicken farm from a mudslide.
- Unnamed Marine Colonel – In "Monkey Fist Strikes", he gives Kim a ride to Cambodia in a military transport plane after she tips him off to an incoming assault.
Drew Theodore P. Lipsky or commonly known as Dr. Drakken (voiced by John DiMaggio; portrayed by Todd Stashwick in the live-action film)[5] is a mad scientist and Kim's archenemy. He is a capable inventor, but is clueless at making his inventions work correctly, and his plans are often undone by his own oversights.
Even though Drakken claims to be evil, at times he has shown a good side and helped Kim save the world. He frequently encounters Kim and Ron, and is always surprised to see Kim even though he is unsure why; as well, he never remembers Ron's name. However, in "The Twin Factor," he does remember his name, and Ron forces him to remember it at the end of So the Drama. In "Graduation", he plays a major role in defeating the Lorwardians and receives a UN medal for it, and he and Shego affirm their love for one another.
Shego (voiced by Nicole Sullivan; portrayed by Taylor Ortega in the live-action film)[5] is Dr. Drakken's sidekick and Kim's most dangerous enemy. She used to be a superheroine alongside her brothers as part of Team Go, as they were hit by a mysterious rainbow "comet" when they were younger and each gained a color-coded glowing superpower; Shego is green-themed and can generate concussive energy blasts.
Initially, Shego was meant to simply be Drakken's sidekick.[6] However, after hearing Nicole Sullivan's performance as Shego, they started to develop her relationship with Drakken, although it is only explicitly identified as a romantic one in the series finale. Sullivan portrayed Shego as sarcastic and more intelligent than Drakken, which became a major aspect of her character.[7]
Lord Monty Fisk, better known as Monkey Fist (voiced by Tom Kane) is a British nobleman and archaeologist who trained to become a master martial artist and underwent procedures from DNAmy to replace his hands and feet with those of a monkey. He is obsessed with increasing his power through various mystical artifacts and prophecies. He is often accompanied by his highly trained Monkey Ninjas who help him in his schemes.
Duff Killigan (voiced by Brian George) is a Scottish villain and the self-proclaimed "World's Deadliest Golfer", who was banned from every golf course in the world because of his temper. He wields golf clubs and exploding golf balls. Although he debuted as an independent villain, subsequent appearances show him as more of a mercenary, committing robberies to sell stolen objects to others. Killigan resides on a private island dubbed "Killigan's Island" in a reference to Gilligan's Island.
- Señor Senior, Sr. (voiced by Ricardo Montalbán, later Earl Boen) is a retired Spanish multi-billionaire who takes up villainy as a hobby at Ron's suggestion. Many of his schemes revolve around acquiring power or influence for his son, Junior, and his tactics usually involve clichés of villainy such as evil laughter and elaborate traps. He is often seen reading and referencing The Book of Evil guidebook, and aims to gain control of Europe. He was an action sports icon in his youth, and has shown that he is quite skilled and spry for his age.
- Señor Senior, Jr. (voiced by Néstor Carbonell) is Senior Sr.'s son and accomplice, a spoiled man-child who is more interested in parties and beauty than his father's criminal plans and has demonstrated a soft side on various occasions. He once had a crush on Kim because of the zodiac-like principles of Animology.
Professor Dementor (voiced and portrayed by Patton Oswalt)[4] is a German mad scientist and rival of Dr. Drakken.
Amy Hall or DNAmy (voiced by Melissa McCarthy) is a geneticist and an avid collector of Cuddle Buddies, which are small stuffed toys similar to Beanie Babies that are hybrids between two animals, with her favorite being the butterfly-otter hybrid Otterfly. In her obsession, she creates mutant animal hybrids which ended up getting her fired and shunned by the scientific community as her splicing experiments were deemed unethical. It also revealed she provided Monkey Fist with his monkey limbs.
Motor Ed (voiced by John DiMaggio) is Dr. Drakken's cousin, who Mrs. Lipsky considers to be the family's "black sheep", and is known for his repetitive use of the words "Dude" and "Seriously!". He has a biker gang motif and is a male chauvinist with an eye for beautiful women.
Camille Léon (voiced by Ashley Tisdale) is an heiress and socialite who became a villain after being cut off from her family fortune and gained shapeshifting abilities after having experimental plastic surgery. Her name is a play on the word chameleon. Unlike other villains, who aim for world domination, Camille commits crimes to fund her lavish lifestyle or out of spite and revenge.
Frugal Lucre (voiced by Richard Kind) is an employee of a Philadelphia Smarty Mart who was originally named Francis Lurman. In the episode "Low Budget", he threatens to destroy the Internet with a destructive virus unless everyone in the world agrees to pay him a dollar each. He is a cost-conscious and budget-minded villain, and so does not use henchmen or a lair. He conducts his evil plans from his mother's basement and threatens his foes with snapping turtles.
Synthodrone #901 (voiced by Raviv Ullman), also known as Eric, is an android created by Dr. Drakken to distract Kim from his plans of world domination. He is later destroyed by Rufus.