Scientist Ben (Zach Galifianakis) belongs to a secret department of the U.S. government. It uses high-tech means to train guinea pigs to speak and think, and trains them into agents. However, Ben's department is facing the situation of being closed by the FBI. In order to prove his and the guinea pig agents' abilities, Ben orders Darwin (voiced by Sam Rockwell), the head of the guinea pig agent team, to sneak into the office of Ronald Seber (Bill Nighy), CEO of Seberlin Industries, to find evidence that Ronald sold high-tech chips that can be used for military purposes to Middle Eastern countries. Darwin did not hesitate, and quickly took members such as Blast (voiced by Tracy Morgan), Wallace (voiced by Penélope Cruz), Fly Mochi and Spex (voiced by Nicolas Cage) to take action. Although this group of guinea pig agents are small in size, they have special skills. They successfully broke into Ronald's office and downloaded important information. However, this adventure has just begun...