Tobey Maguire (Peter Parker / Spider-Man), Kirsten Dunst (Mary Jane Watson), James Franco (Harry Osborn), Alfred Molina (Otto Octavius / Doctor Octopus), Rosemary Harris (May Parker), J.K. Simmons (J. Jonah Jameson), Donna Murphy (Rosalie Octavius) more..., Dylan Baker (Dr. Curt Connors), Daniel Gillies (John Jameson), Bill Nunn (Joseph 'Robbie' Robertson), Vanessa Ferlito (Louise), Aasif Mandvi (Mr. Aziz), Willem Dafoe (Norman Osborn), Cliff Robertson (Ben Parker), Ted Raimi (Hoffman), Elizabeth Banks (Miss Brant), Bruce Campbell (Snooty Usher), Gregg Edelman (Dr. Davis), Elya Baskin (Mr. Ditkovich), Mageina Tovah (Ursula), Daniel Dae Kim (Raymond), Hal Sparks (Elevator Passenger (uncredited)), Joel McHale (Mr. Jacks), Stan Lee (Man Dodging Debris (uncredited)), Kelly Connell (Dr. Isaacs), Brent Briscoe (Garbage Man (uncredited)), Emily Deschanel (Receptionist (uncredited)), Jason Fiore-Ortiz (Henry Jackson), Scott Spiegel (Man on Balcony (uncredited)), Andy Bale (OsCorp Executive), Christine Estabrook (Mrs. Jameson), Molly Cheek (Society Woman (uncredited)), John Paxton (Houseman (uncredited)), Joy Bryant (Woman at Web (uncredited)), Joanne Baron (Skeptical Scientist (uncredited)), Peter McRobbie (OsCorp Representative (uncredited)), Timothy Jerome (Injured Scientist (uncredited)), Taylor Gilbert (Mrs. Watson (uncredited)), Peter Vouras (Stage Manager (uncredited)), Donnell Rawlings (Pizza 'Heist' Witness (uncredited)) and others.

Danny Elfman (Original Music Composer), Dianne Crittenden (Casting), Bill Abbott (Music Editor), Jay Hart (Set Decoration), Joseph M. Caracciolo Jr. (Executive Producer), John Frazier (Special Effects Supervisor), Kristen Branan (Head of Production) more..., Stan Lee (Executive Producer), Stan Lee (Comic Book), Steve Ditko (Comic Book), Bob Murawski (Editor), Laura Ziskin (Producer), Avi Arad (Producer), Neil Spisak (Production Design), James Acheson (Costume Design), Alvin Sargent (Screenplay), Lorne Orleans (Producer), Kevin Feige (Executive Producer), Bill Pope (Director of Photography), Grant Curtis (Co-Producer), Christopher Young (Original Music Composer), Dan Bradley (Stunt Coordinator), Dan Bradley (Second Unit Director), Hank Amos (Stunts), Hank Amos (Utility Stunts), Thomas P. Wilkins (Art Direction), Scott G.G. Haller (Sound Editor), Thomas Valentine (Art Direction), Danny Cangemi (Special Effects Coordinator), Jim Passon (Color Timer), Joseph M. Caracciolo (Executive Producer), Greg P. Russell (Sound Re-Recording Mixer), Miles Millar (Screenstory), Alfred Gough (Screenstory), John Dykstra (Visual Effects Supervisor), John Dykstra (Visual Effects Designer), Timothy Healy (Electrician), François Audouy (Graphic Designer), Steve Saklad (Art Direction), Steve Bartek (Additional Music) and others.