Onder andere met: Andrew Garfield (Spider-Man / Peter Parker), Emma Stone (Gwen Stacy), Rhys Ifans (The Lizard / Dr. Curt Connors), Denis Leary (Captain Stacy), Martin Sheen (Uncle Ben), Sally Field (Aunt May), Irrfan Khan (Rajit Ratha), Campbell Scott (Richard Parker), Embeth Davidtz (Mary Parker), Chris Zylka (Flash Thompson), Max Charles (Peter Parker (Age 4)), C. Thomas Howell (Jack's Father), Jake Keiffer (Jack), Kari Coleman (Helen Stacy), Michael Barra (Store Clerk), Andy Pessoa (Gordon), Kelsey Chow (Hot Girl), Barbara Eve Harris (Miss Ritter), Kevin McCorkle (Mr. Cramer), Tom Waite (Nicky), Danielle Burgio (Nicky's Girlfriend), Amber Stevens (Ariel), Tia Texada (Sheila)