The cast of the animated series "Big Mouth" includes a talented ensemble of adult comedians who voice the adolescent characters and various other roles. Key cast members are:

• Nick Kroll as Nick Birch and various other characters; he is also one of the creators.
• John Mulaney as Andrew Glouberman.
• Jessi Klein as Jessi Glaser.
• Jason Mantzoukas as Jay Bilzerian.
• Maya Rudolph as various female characters including hormone monsters.
• Jordan Peele also voices several characters.
• Additional notable voice actors include Nick Kroll, John Mulaney, Jessi Klein, Jason Mantzoukas, Maya Rudolph, Jordan Peele, Andrew Rannells, Joe Wengert, Richard Kind, Jessica Chaffin, Gil Ozeri, Neil Casey, and Thandiwe Newton.

The show features recurring voices for hormone monsters, parents, and other school characters, with guest and recurring stars such as Megan Thee Stallion and Lupita Nyong'o in later seasons. The series has released eight seasons, concluding in 2025, and also spawned a spin-off titled "Human Resources".