Helen Stewart is Wing Governor of G-Wing, whose authority is seldom respected by the prisoners. After a personal struggle with her sexuality, the battle to stand as an authority figure in Larkhall, and the breakup from her fiancé Sean, she goes on holiday to clear her head. After a delay in her flight, Helen is replaced by Jim Fenner. She returns shortly after but leaves. She returns to work with prisoners serving life sentences, is sexually assaulted by Jim, and struggles with coming to terms with her sexuality. She falls in love with prisoner Nikki Wade. When Simon is demoted after Shell Dockley, Denny Blood, and Shaz Wylie escape, Helen becomes the new acting governor of Larkhall. Her feud with Jim comes to a head and she resigns before she is sacked.

Nikki Wade is serving a life sentence for killing a policeman who tried to rape her then-girlfriend Trisha. An out and proud lesbian, Nikki is an outspoken strong-minded inmate who clashes with Helen at the start of the series. Hated by Jim, Nikki is respected by most of the other inmates apart from Shell. The pair frequently clash over Shell's relationship with Jim and the fact that Nikki is not impressed or intimidated by Shell. After being dumped by Trisha, Nikki falls for Helen and escapes from Larkhall in the series 2 finale before the two have sex. However, Helen refuses to run away with Nikki and returns her to prison and briefly ends their relationship. Nikki organises a peaceful protest when some of the officers brutally restrain Femi Bada, a non-English speaking inmate who is separated from her kids, which escalates into a riot and Helen ends their relationship again, though she continues to help her with her appeal. At the end of series 3, Dr Thomas Waugh breaks up with Helen after realising she is in love with Nikki, and Helen reunites with her after she wins her appeal.

Michelle "Shell" Dockley is serving life for the kidnap, torture, and murder of the woman who stole her boyfriend. Shell appeared from the first episode in series 1 until series 3 when Shell, Denny Blood and Shaz Wiley escape. During her reign as top dog she bullies inmate Rachel Hicks, which results in her suicide. She also has an affair with Jim, which ends violently when she calls his wife to have her hear them having sex in her cell. When Yvonne Atkins arrives, she takes over as top dog as the women respect her and she is not afraid of Shell. She suffers a breakdown in series two which is brought on by the sexual abuse she suffered as a child from her parents. Shell takes revenge on Jim by luring him into her cell and stabbing him. Although she attempts to claim self-defence, she is charged with assault and attempted murder, but she escapes with Jim's help. Shell and Denny make recurring appearances throughout the remainder of series 3. Shell returns in series 5 when she is found by Jim, Collin Hedges, and Ken Pearce at an erotic dance club where she is performing before being arrested and sent back to Larkhall. She is pregnant and re-enters into a relationship with Jim, which ends when Shell is transferred to a psychiatric hospital shortly after giving birth.

Shell was voted #8 on Virgin Media's "Top 10 TV Criminals".

Jim Fenner is the principal officer of G-Wing, later wing governor, and then acting governor, and is one of the main antagonists of the series. He is a prison officer who bends and breaks rules. At the start of the programme he is portrayed as only slightly corrupt as he still cared for his family, but by series seven, he has killed a few people. He is killed in series 7 by Julie Johnston.

In 1999, Ellis accepted the role without looking at the scripts. He told Yvonne Swann of the Daily Mirror that he had been in debt, welcomed the role, and that "it certainly put [his] name on the map" as an actor.

Danielle "Denny" Blood is the enforcer and occasional lover of Shell. She is initially portrayed as thuggish and cruel but later develops to be somewhat caring and kind, especially to her girlfriend Shaz. When Shaz is accidentally killed in a fire, Denny seeks revenge on Snowball Merriman, an inmate who causes the fire during her escape. Denny later bonds with Yvonne Atkins.

Rachel Hicks is a 19-year-old girl who is serving over a year in prison for possession of drugs. She has a baby daughter named Maddie, who is taken in by her mother after her arrest. Rachel's mother puts Maddie into foster care as she is unable to look after her and wanted her life back. Rachel kills herself in the middle of series 1 after being bullied.