Spider-Man When transforming into Spider-Man, he wears a red and blue spandex suit and mask. He is a hero with many fans, yet no one knows his true face. He has a kind personality but is occasionally swayed by his emotions. This is Peter four years after the events of No Way Home. Due to Doctor Strange's spell, all memory of Peter Parker has vanished from the world, and even MJ and Ned do not remember him. Consequently, this version of Peter is much lonelier and more independent, living alone while spending almost all his time fighting crime in New York. However, strange changes begin to occur in his body, causing his spider-powers to become unstable and his aggression to increase.

Punisher Frank Castle, played by Jon Bernthal, returns as the Punisher. Because he deals with criminals in a fundamentally different way than Spider-Man, the two often clash. While Peter is a hero focused on saving people, Frank is a character who fights crime in a much harsher and colder manner. Having lost his family in the past, he is never swayed by emotional pleas. He operates under the mindset that "scumbags who do wrong deserve to die," and nearly all his expressions are blunt and rough.

MJ She is the person Peter loved most, but she has no memory of him. In this story, rather than being just Peter's lover, MJ is a crucial figure who makes Peter reflect on his own life. Peter wants to get close to MJ again, but since he cannot reveal his identity immediately, he has to rebuild their relationship as if they were meeting for the first time. She is intelligent but occasionally shows a quirky, eccentric side.

Ned Leeds Ned was once Peter's best friend. He also does not remember Peter. However, he becomes involved with Peter again and uses his unique technical skills to create a device capable of tracking Spider-Man. This device plays a very significant role in the latter half of the story. He has a fun and humorous personality.

He leads the Department of Damage Control. On the surface, it appears to be a clean, large government agency consisting of labs and offices that handle superhuman incidents. However, in the basement, they conduct dangerous research and experiments on mutants. No one suspects Bill Metzger of any wrongdoing. He carries out high-risk research to grant or strip away superpowers—such as those belonging to Jean Grey's family—for the benefit of those he chooses.

Jean Grey Played by Sadie Sink, this character is revealed in the latter half to be the MCU's Jean Grey. This marks the full-scale introduction of mutants and the X-Men into the MCU setting. Jean possesses incredibly powerful telepathic abilities and can influence the minds and bodies of others. Initially appearing as a simple antagonist, her true objective was to save her family member, Sara.