Anne's relationship with her older sister Margot is complex. Initially, Anne looks up to Margot, but as they mature, a degree of sibling rivalry develops. In the annex, Margot is often seen as more reserved and studious, while Anne is more outgoing and rebellious. Despite their differences, they share a deep bond, evident in Anne's diary entries where she expresses concern for Margot's well-being.

Anne has a very close and loving relationship with her father, Otto Frank, whom she affectionately calls 'Pim.' He is a source of comfort, guidance, and support for her, especially during the difficult years in hiding. Otto encourages Anne's writing and believes in her potential.

Anne's relationship with her mother, Edith Frank, is more strained. Anne finds her mother to be less understanding and more critical than her father. This tension is exacerbated by the confined living conditions in the annex, leading to frequent arguments and misunderstandings. Anne often expresses feelings of guilt for not being closer to her mother.

In the annex, Anne develops a romantic interest in Peter van Pels, the teenage son of Hermann and Auguste van Pels. Their relationship provides comfort and companionship during their confinement, and Anne experiences her first feelings of love and affection. However, their relationship is also marked by youthful awkwardness and uncertainty.

Lies Goosens, later known as Hanneli Goslar, was one of Anne's closest friends before the war. They attended school together and shared many happy memories. After going into hiding, Anne often thinks of Lies and wonders about her fate. Lies later survives the Holocaust and recounts her memories of Anne, providing valuable insights into Anne's personality and pre-war life.

Jacqueline van Maarsen was another of Anne's close friends in Amsterdam. Although Jacqueline was not Jewish (her mother was Christian), she also experienced discrimination due to her mother's heritage. Their friendship provides insights into Anne's social life and the impact of anti-Jewish measures on friendships.

Anne's relationship with Auguste van Pels is complex and often strained. Anne finds Auguste to be vain and superficial, and the two often clash over personality differences and living arrangements in the annex. Anne's diary provides a candid portrayal of their interactions.

Anne's relationship with Hermann van Pels is generally more neutral. While she observes and comments on his behavior in her diary, there isn't the same level of direct conflict as with Auguste. She notes his business acumen and occasional grumpy demeanor.

Anne's relationship with Fritz Pfeffer, with whom she shares a room in the Annex, is contentious. She finds him annoying, rigid, and overly critical. Their shared living space intensifies their personality clashes, and Anne often expresses her frustration with him in her diary.