| Tobey Maguire - Peter Parker / Spider-Man |
| Kirsten Dunst - Mary Jane Watson |
| James Franco - Harry Osborn / New Goblin |
| Thomas Haden Church - Flint Marko / Sandman |
| Topher Grace - Eddie Brock / Venom |
| Bryce Dallas Howard - Gwen Stacy |
| Rosemary Harris - May Parker |
| James Cromwell - Captain Stacey |
| J.K. Simmons - J. Jonah Jameson |
| Theresa Russell - Mrs. Marko |
| Dylan Baker - Dr. Curt Connors |
| Bill Nunn - Joseph Robertson |
| Elizabeth Banks - Miss Brant |
| Ted Raimi - Hoffman |
| Perla Haney-Jardine - Penny Marko |
| Willem Dafoe - Norman Osborn / Green Goblin |
| Cliff Robertson - Ben Parker |
| Elya Baskin - Mr. Ditkovitch |
| Mageina Tovah - Ursula |
| Michael Papajohn - Dennis Carradine / Carjacker |
| Joe Manganiello - Flash Thompson |
| Stan Lee - Man in Times Square |
| Bruce Campbell - Maître d |
| Christopher Young - Pianist |
| Grant Curtis - Driver |
| Daniel Gillies - John Jameson |
| John Paxton - Houseman |
| Becky Ann Baker - Mrs. Stacy |
| Steve Valentine - Photographer |
| Hal Fishman - Anchorman |
| Lucy Gordon - Jennifer Dugan |
| Toni Wynne - Congratulatory Woman at Daily Bugle |
| Andre B. Blake - Crane Disaster Radio Policeman |
| Tim Maculan - Play Director |
| Marc Vann - Play Producer |
| Joe Bays - Jazz Club Manager |
| Gregg Daniel - Precinct Detective |
| Rogelio T. Ramos - Emergency Room Doctor |
| Timothy Patrick Quill - Crane Operator |
| Kathryn Bryding - Woman Outside Theater |
| Joe Virzi - Police Detective |
| Bill E. Rogers - New Jersey State Policeman |
| Michael Alexander - New Jersey State Policeman |
| April Parker-Jones - Test Site Technician |
| Edward Padilla - Test Site Technician |
| Robert Curtis Brown - Test Site Technician |
| Paul Terrell Clayton - Test Site Technician |
| Carolyn Neff - Test Site Technician |
| Christina Cindrich - Test Site Technician |
| Sonya Maddox - ICU Nurse |
| Derrick 'Phoenix' Thomas - Cop at Crane Disaster |
| Jessi Collins - Mary Jane's Replacement |
| Michael McLaughlin - Boy at Key to the City Ceremony |
| Anne Gartlan - Councilwoman |
| Emilio Rivera - Policeman at Sand Truck |
| Keith Woulard - Policeman at Sand Truck |
| Reynaldo Gallegos - Armored Car Driver |
| Jim Coope - Newstand Patron |
| Dean Edwards - Newstand Patron |
| Margaret Laney - Newstand Patron |
| Aimee Miles - Coffee Shop Waitress |
| Tanya Bond - Jazz Club Waitress |
| Mark Kubr - Jazz Club Bouncer |
| Tony Besson - Photoshoot Client |
| Ramon Adams - Businessman (uncredited) |
| A.J. Adelman - Theater Attendee (uncredited) |
| Angelis Alexandris - Pedestrian (uncredited) |
| Dawn Marie Anderson - I.C.U Nurse (uncredited) |
| Frank Anello - NYPD Officer (uncredited) |
| Anya Avaeva - Model (uncredited) |
| David Backus - Bucket Boy (uncredited) |
| Tiffany L. Baker - News Reporter (uncredited) |
| Marc C. Cancassi - Photographer (uncredited) |
| Sujeilee Candele - Rescued Girl (uncredited) |
| Michael Ciesla - Photographer (uncredited) |
| Irina Costa - Jazz Club Waitress (uncredited) |
| John Crann - Theater Patron (uncredited) |
| Crystal Marie Denha - Jazz Club Girl (uncredited) |
| Amy V. Dewhurst - Columbia Grad Student (uncredited) |
| Paul Edney - New York City Commuter / Driver (uncredited) |
| Natalie Fabry - Girl at Key Ceremony (uncredited) |
| Keith Fausnaught - Pedestrian (uncredited) |
| Amanda Florian - A Spidey Kid (uncredited) |
| Brianna Leann Florian - A Spidey Kid (uncredited) |
| Tiffany Ashley Florian - A Spidey Kid (uncredited) |
| Shaun Patrick Flynn - Businessman (uncredited) |
| Logan Fry - Automobile Driver (uncredited) |
| Kevin Fung - Spectator (uncredited) |
| Tony Galtieri - News Spectator (uncredited) |
| Chuck Gerena - Funeral Limo Driver (uncredited) |
| Brian Hopson - News Reporter (uncredited) |
| Claude Jay - Cop (uncredited) |
| Julie Jei - Female New Yorker (uncredited) |
| Andrew James Jones - Jazz Club Bouncer (uncredited) |
| Natalie Jones - Girl at Key Ceremony (uncredited) |
| Christopher Jude - Student (uncredited) |
| Brittany Krall - ER Nurse (uncredited) |
| Alyssa Lakota - Dog Walker (uncredited) |
| Tia Latrell - Observer (uncredited) |
| Linda Lee - Businesswoman (uncredited) |
| Pierangeli Llinas - Woman in Court (uncredited) |
| Bernadette Lords - British Publicist (uncredited) |
| Sandrine Marlier - Shocked Pedestrian (uncredited) |
| Laura McDavid - Journalist (uncredited) |
| Natalie McNeil - Girl Screaming in Camaro (uncredited) |
| Daniel Mignault - Kid in Times Square (uncredited) |
| Martha Millan - Oscorp Receptionist (uncredited) |
| Michele-Nanette Miller - Girl in Times Square (uncredited) |
| Claudia Katz Minnick - Robbie's Assistant (uncredited) |
| Robert Myers - Theatergoer (uncredited) |
| Joseph O'Brien - Businessman (uncredited) |
| Jen Oda - Beautiful Girl (uncredited) |
| Anjelia Pelay - Beautiful Woman (uncredited) |
| Nick Poltoranin - Police Officer (uncredited) |
| Vanessa Reseland - Beautiful Woman (uncredited) |
| La Rivers - Beautiful Woman (uncredited) |
| Bria Roberts - Businesswoman (uncredited) |
| Luis Rosa - Pedestrian (uncredited) |
| Vanessa Ross - Sandman Victim (uncredited) |
| Brenna Roth - Bad Girl (uncredited) |
| Shade Rupe - City Hall Cheerer (uncredited) |
| Arick Salmea - Guy with Ticket (uncredited) |
| Eric Shackelford - Jazz Club Beatnik (uncredited) |
| Daniel Shafer - Jazz Club Guest (uncredited) |
| Abbey Skinner - Café Girl (uncredited) |
| Kristin Somo - Jazz Club Patron (uncredited) |
| Jennifer Sparks - Jazz Club Waitress (uncredited) |
| Christopher Stadulis - Firefighter (uncredited) |
| Jimmy Star - Police Officer (uncredited) |
| Arne Starr - Broadway Audience Member (uncredited) |
| Liam Stone - Jazz Club Musician (uncredited) |
| Tajna Tanovic - Girl in Cab (uncredited) |
| Aija Terauda - Model (uncredited) |
| Brigid Turner - Hot Girl (uncredited) |
| Evelyn Vaccaro - Beautiful Woman (uncredited) |
| Nick Vlassopoulos - Bar Patron #5 (uncredited) |
| Sincerely A. Ward - Model (uncredited) |
| Silq Webster - Model (uncredited) |
| Graig F. Weich - Student (uncredited) |
| Fredrick Weiss - Restaurant Patron (uncredited) |
| Jennifer Weston - ER Nurse (uncredited) |
| Trenton Willey - City Hall Cheerer (uncredited) |
| Ray Wineteer - Spectator (uncredited) |
| Emily Eckes - Beautiful Woman (uncredited) |
