| Rolle | Person |
|---|---|
| Dr. Otto Octavius / Doc Ock | Dirk Hardegen |
| Felicia Hardy / Black Cat | Lara „Loft“ Trautmann |
| J. Jonah Jameson | Hanns Jörg Krumpholz |
| Jefferson Davis | Michael-Che Koch |
| Martin Li / Mister Negative | Florian Hoffmann |
| Mary Jane „MJ“ Watson | Johanna Dost |
| Miles Morales | Lars Waltl |
| Peter Parker / Spider-Man | Felix Mayer |
| Silver Sablinova / Silver Sable | ??? |
| Tante May Parker | ??? |
| Yuriko „Yuri“ Watanabe | Yesim Meisheit |
| Rolle | Person |
|---|---|
| Adrian Toomes / Vulture | Richard van Weyden |
| Aleksei Sytsevich / Rhino | Christian Jungwirth |
| Bauarbeiterin | ??? |
| Charles Standish | Peter Dischkow |
| David Obademi im DLC »Die Stadt, die niemals schläft« | Daniel Welbat |
| Dr. Morgan Michaels | Dieter Gring |
| Gloria Davila | ??? |
| Harry Osborn | Nils Kreutinger |
| Herman Schultz / Der Shocker | Mario Hassert |
| Howard, der Taubenfütterer | Achim Barrenstein |
| Isaac Delaney | ??? |
| Joseph Martello / Hammerhead im DLC »Die Stadt, die niemals schläft« | ??? |
| Lonnie Lincoln / Tombstone | Tobias Brecklinghaus |
| MacDonald „Mac“ Gargan / Scorpion | Michael-Che Koch |
| Maxwell „Max" Dillon / Electro | ??? |
| Norman Osborn | ??? |
| Obdachlose | ??? |
| Restaurantkoch / Stan Lee | ??? |
| Rio Morales | Gisa Bergmann |
| Rose Rosemann | Nora Jokhosha |
| Screwball | Leyla Trebbien |
| Stephanie | Nora Jokhosha |
| Taskmaster | Dieter Gring |
| Walter Hardy / Detective Mackey im DLC »Die Stadt, die niemals schläft« | Steffen Wilhelm |
| Wilson Fisk / Kingpin | Thomas Balou Martin |