•
Antonio Banderas as Gregorio Cortez, Head of the OSS and father of Juni and Carmen •
Carla Gugino as Ingrid Cortez, also an OSS agent and mother of Juni and Carmen •
Alexa Vega as
Carmen Cortez, daughter of Gregorio and Ingrid, OSS agent and Juni's older sister who goes missing •
Daryl Sabara as
Juni Cortez, Carmen's younger brother, and a retired OSS agent turned private detective who is called out of retirement to rescue her •
Ricardo Montalbán as Valentin Avellan, Juni and Carmen's maternal grandfather and Ingrid's father, who is a retired OSS agent himself •
Holland Taylor as Helga Avellan, Juni and Carmen's maternal grandmother and Ingrid’s mother •
Mike Judge as Donnagon Giggles, an OSS former director, now technician who was formerly the previous film's antagonist •
Matt O'Leary as Gary Giggles, the son of Donnagon Giggles and a former competing OSS agent who assists Carmen in the final battle •
Emily Osment as Gerti Giggles, the daughter of Donnagon Giggles, Gary's sister, a former competing OSS agent, and Juni's closest friend, who assists Juni and Carmen in the final battle •
Cheech Marin as Felix Gumm, OSS agent and Carmen and Juni's honorary uncle •
Bobby Edner as Francis, a Game Over contestant and one of Juni's rivals and teammates in Game Over •
Courtney Jines as Demetra, a Game Over program known as "The Deceiver" who is also Juni's rival and crush in Game Over. •
Ryan Pinkston as Arnold, a Game Over contestant and one of Juni's teammates and rivals in Game Over • Robert Vito as Rez, a Game Over contestant and one of Juni's teammates and rivals in Game Over •
Danny Trejo as
Isador "Machete" Cortez, gadget inventor and uncle of Juni and Carmen who assists them in the climax •
Alan Cumming as Fegan Floop, the host of Floop's Fooglies who assists Carmen and Juni along with their parents in the final battle. He is also shown at the beginning of the 3D version of the movie, giving the viewers instructions on how to put on 3D glasses. •
Tony Shalhoub as Alexander Minion, Floop's assistant still in Floogie form who helps Carmen and Juni in the climax •
Sylvester Stallone as Agent Sebastian "The Toymaker", a former OSS agent turned
supervillain, and the creator of the virtual reality game, Game Over. Additionally,
Salma Hayek appears as Francesca Giggles, the wife of Donnagan who is keeping him in line after what happened in the last film as she was also mentioned that she dislikes some of his actions;
Steve Buscemi appears as Romero, a scientist and creator of the hybrid animals who assists the Cortez family in the climax;
Bill Paxton appears as Dinky Winks, the owner of the theme park Troublemakers who assists the Cortez family in the climax;
George Clooney appears as Devlin, the President of the United States who was later impersonated by Toymaker;
Elijah Wood appears as The Guy;
Selena Gomez appears as a water park girl that Juni told the reason on why there's no water in the theme park;
Glen Powell appears in his film debut as a long-fingered boy; and
James Paxton appears as Dinky Winks Jr., the son of Dinky Winks who accompanies his father in the climax and witnesses him branding one of Toymakers' giant robots. == Production ==