- Johnny Knoxville as Megamind
- Bam Mergera as Minion
- Ryan Dunn as MetroMan
- Chris Pontius as Hal Stewart
- Dave England as Bernard
- Brandon Novak as Megamind's Dad (cameo)
- Kat Von D as Roxanne (cameo)
- Mark Zupan as Space Dad (cameo)
- John Waters as Mayor (cameo)
- Rip Taylor as The Wardon (cameo)
- and more
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