• Andrew Garfield - Peter Parker / Spider-Man, the main protagonist. He swore to stop every kind of crime after his Uncle Ben died, and since he has spider powers after he got bit by a radioactive spider, Peter must face his biggest enemy: The Vulture.
  • Emma Stone - Gwen Stacy, the love of Peter Parker's life. Her father, Captain Stacy, was killed by Lizard and now she lives in fear of Rhino... believing he's just like a new Lizard.
  • Martin Sheen - Ben Parker, Peter's dead uncle. Peter goes through his memories of Uncle Ben.
  • Sally Field - May Parker, Ben's wife and Peter's aunt. Peter lives with her as she is the last family member he has left. She gives Peter advice along the way and in the end gets kidnapped by The Vulture and The Rhino.
  • Kevin Bacon - Norman Osborn, the millionare founder of Oscorp Industries and the father of Harry Osborn. He is rude and ignorrant, and Vulture wants revenge on him for it.
  • Charles Dance - Adrien Tombes / The Vulture, a former Oscorp employee who quit after his "Vulture-Glider" idea was rejected. He continued his work at home and used the Glider to get revenge on Norman Osborn. Vulture is the main antagonist.
  • Adam Baldwin - Aleksei Sytsevich / The Rhino, a former soldier who volunteered for Norman Osborn's project at Oscorp, but accidently got stuck in a cement suit now bonded to his flesh. The suit resembles a Rhino, and is invulnerable and super strong. Rhino used it to get revenge on Norman Osborn, and teamed up with another Osborn-hating villain, The Vulture, to get said revenge.
  • Kevin McHale as Harry Osborn - Peter's new best friend and Norman Osborn's son.Harry gets kidnapped by Vulture along with Aunt May, as bait for Norman Osborn and Peter Parker.
  • Asa Buterfield - Younger Peter Parker, he appears in a flashback

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