Onder andere met: Tobey Maguire (Spider-Man/Peter Parker), Willem Dafoe (Green Goblin/Norman Osborn), Kirsten Dunst (Mary Jane Watson), James Franco (Harry Osborn), Cliff Robertson (Uncle Ben), Rosemary Harris (Aunt May), J.K. Simmons (J. Jonah Jameson), Joe Manganiello (Flash Thompson), Gerry Becker (Maximilian Fargas), Bill Nunn (Joseph `Robbie` Robertson), Jack Betts (Henry Balkan), Stanley Anderson (General Slocum), Ron Perkins (Dr. Mendell Stromm), Michael Papajohn (Carjacker), K.K. Dodds (Ellie Simkins), Robert Kerman (Tugboat Captain), Scott Spiegel (Marine Cop), Lucy Lawless (Punk Rock Girl), Bruce Campbell (Ring Announcer)