- Tobey Maguire: I've had a lot of fun playing Spider-Man/Peter Parker in all three of the films and what I think we've done really well is to make each film its own unique movie and therefore it's been really exciting and a lot of fun for me as an actor to show up because it's like a brand new character in a sense.
- Bruce Campbell: Hi, gang. I'm Bruce Campbell. I'm playing the narrator of the Spider-Man 3 game. And let me tell you all about it. Ok, there's this guy named Spider-Man and he flips around and spins stuff and catches bad guys. So go.
- [beat]
- Bruce Campbell: No, go!
- James Franco: Harry is trying to figure out who Spider-Man is and he's bent on vengeance but once he finds out that it's Peter, he's kind of taken it back but you see him in the third film and he's gotten over that and doesn't matter if it's his best friend he's ready to kill.
- Chris Archer: Creating Spider-Man 3 is a pretty amazing experience. You take all of the previous games and the great response from those and what you want to do is give Spider-Man fans and Spider-Man players the best Spider-Man experience that they can possibly get.
- Thomas Haden Church: Flint Marko and Peter Parker actually quite have a lot in common because they both represent a darker, malevolent force that cannot be entirely controlled. Once it's conjured, it really has the capability of wreaking terrific physical harm and damage.
- J.K. Simmons: Spider-Man 3 is really more involved. There's more going on than maybe in the first two movies combined. Lots of new characters, new bad guys, new side characters and new female character that Peter Parker deals with. It's just a lot of stuff going on. Lots of fun, lots of carnage, lots of fights, lots of screaming from the boss.
- Topher Grace: I play Eddie Brock who becomes Venom and Eddie is very similar to Peter. When the movie starts, they both have the same job. They both work at the Bugle and they're both kind of after the same woman.