As a child, Peter Griffin befriends a talking dog named Brian. 30 Years later, he and Brian spend the rest of their lives, hanging out with friends and family. But when Brian is kidnapped by a fugitive, Peter and his friends go on a mission to save Brian.
In 1982, 12-year-old Peter Griffin (David Mazouz) is an outcast that is not popular in his town called Quahog, a city filled with comedy. When goes home, he finds a injured dog in the trash and names him Brian. Before he goes to bed, he wishes Brian can talk and the next morning, the wish came true that Brian can talk and has the mind of a human. Peter and Brian are now brothers.
- John Goodman as Peter Griffin - The Protagonist of the film.
- David Mazouz as 12-year-old Peter Griffin.
- Julianne Moore as Lois Griffin - Peter's wife and the Tritagonist of the film.
- Camren Bicondova as 12-year-old Lois Griffin.
- Odeya Rush as Meg Griffin - Peter's older daughter.
- Jeremy Ray Taylor as Chris Griffin - Peter's son.
- A 1 year-old baby will play as Stewie Griffin - Peter's younger son.
- Kevin Spacey as Stewie's voice
- Seth MacFarlane as Brian Griffin (voice) - The Deuteragonist of the film and Peter's step-brother.
- Patrick Stewart as The Narrator.
- Tobey Maguire as Tom Tucker
- Cameron Diaz as Joyce Kinney
- Ice Cube as Cleveland Brown
- Tyrel Jackson Williams as 11-year-old Cleveland Brown.
- Willem Dafoe as Glenn Quagmire - Peter's dirty neighbor and former coach.
- Patrick Warburton as Joe Swanson
- Tia Mowry as Donna Tubbs-Brown
- Cobie Smulders as Bonnie Swanson
- Spencer Boldman as Kevin Swanson
- TBA as Suzy Swanson
- Anthony Anderson as Cleveland Brown, Jr
- A five-year-old African-American baby as Rallo Tubbs
- Kevin Michael Richardson as Rallo's voice
- Zendaya as Roberta Tubbs
- Fan Bingbing as Tricia Takanawa
- Anthony rogers as tricia's boyfriend
- Neil Patrick Harris as Mort Goldman
- Zachary Gordon as Neil Goldman
- Emily Deschanel as Diane Simmons
- Robert Joy as Seamus Levine
- Leslie Jordan as Herbert
- Terry Crews as Jerome
- Adam West as Himself - An actor turned mayor of Quahog.
- Clancy Brown as Carter Pewterschmidt - The Tertiary Antagonist of the film and Lois' abusive step-father.
- TBA as Barbara "Babs" Pewterschmidt
- Madison Lintz as Connie D'Amico
- Laurence Fishburne as Ollie Williams
- Adam Carolla as Death (voice)
- Matt Damon as Ernie the Giant Chicken (voice) - The Secondary Antagonist of the film and Peter's rival.
- Jessica Barth as Jillian Wilcox - Brian's girl-friend.
- Raymond Ochoa as Jake Tucker
- Breckin Meyer as Dr. Hartman
- James Wolk as Principal Shepard
- Marissa Tomei as Carol West
- Jimmy Fallon as Al Harrington
- James Woods as Himself
Main Cast Gallery
- Adam West, Seth MacFarlane and Danny Smith reprises their role from the series
- Raymond Ochoa will dye his hair blonde for his role.
- Julianne Moore will dye her hair orange for her role.
- Peter Griffin is skinny in this one.
- TBA will practice singing for the Peter Griffin role.
- Julianne Moore, Tobey Maguire and Cameron Diaz will practice singing for the role.
- Michael Cera will have blond hair for his role as Chris.
- Carter is instead Lois' step-father in the film.