 | Brad Pitt | | Mills |
| Morgan Freeman | | Somerset |
| Kevin Spacey | | John Doe |
| Gwyneth Paltrow | | Tracy |
| Andrew Kevin Walker | | Dead Man at 1st Crime Scene |
| Daniel Zacapa | | Detective Taylor at First Murder |
| John Cassini | | Officer Davis |
| Bob Mack | | Gluttony Victim |
| Peter Crombie | | Dr. O'Neill |
| Reg E. Cathey | | Dr. Santiago |
| R. Lee Ermey | | Police Captain |
| George Christy | | Workman at Door of Somerset's Office |
| Endre Hules | | Cab Driver |
| Hawthorne James | | George the Night Guard at the Library |
| Mark Boone Junior | | Greasy F.B.I. Man |
| William Davidson | | First Guard at the Library |
| Bob Collins | | Second Guard at the Library |
| Jimmy Dale Hartsell | | Library Janitor |
| Richard Roundtree | | Talbot |
| Charline Su | | TV News Reporter |
| Dominique Jennings | | TV News Reporter |
| Allan Kolman | | First Forensic Man in the Law Office |
| Beverly Burke | | TV Anchor Woman |
| Gene Borkan | | Eli Gould - Greed Victim |
| Julie Araskog | | Mrs. Gould |
| Mario Di Donato | | Fingerprint Forensic Man in Law Office |
| Alfonso Freeman | | Fingerprint Technician |
| John C. McGinley | | California |
| Harrison White | | Cop on SWAT Team |
| Bob Stephenson | | Cop on SWAT Team |
| Michael Reid MacKay | | Victor - Sloth Victim |
| Richard Portnow | | Dr. Beardsley |
| Tudor Sherrard | | Coupon Man Outside Pizza Parlor |
| Pamala Tyson | | Thin Vagrant by John Doe's Apartment |
| Lennie Loftin | | Policeman Who Takes Statement from Vagrant |
| Sarah Reinhardt | | Police Sketch Artist |
| Emily Wagner | | Detective Sara at John Doe's Apartment |
| Martin Serene | | Wild Bill |
| Michael Massee | | Man in Booth at Massage Parlor |
| David Correia | | First Cop at Massage Parlor |
