Sergeant Keroro, a frog-like alien from the planet Keron, is the leader of a platoon sent on a mission to conquer Earth, a planet they call Pekopon. The plan goes awry when Keroro is discovered and captured by the Hinata family. Rather than face a hostile reception, he ends up living in their home, where he is effectively treated as a guest who must perform household chores in exchange for his keep. His grand ambitions of invasion are continuously sidelined by his own laziness, his love for building Gundam plastic models, and the ever-present threat of the family's fierce daughter, Natsumi, who serves as the unofficial defender of the household.

The series is set primarily in the city of Tokyo, revolving around the daily lives of the Hinata family and the Keroro Platoon, which operates from a secret base built in the basement of the family's home. The main human characters include Fuyuki Hinata, a gentle and curious middle school boy fascinated by the paranormal who becomes Keroro's master, and his older sister Natsumi, an athletic and hot-headed girl who is constantly vigilant against the platoon's schemes. Their mother, Aki, is a manga editor who is largely unfazed by the aliens and often encourages their outlandish behavior for the sake of a good story.

The Keroro Platoon is comprised of five distinct personalities, each with their own military specialty and quirks. Tamama is an energetic yet jealous private who has a fierce rivalry with anyone who gets close to Keroro. Giroro is a hot-blooded weapons specialist who secretly harbors a crush on Natsumi. Kururu is a sadistic and cunning technical genius who invents a wide array of gadgets. Dororo is a ninja-like warrior who was once a fearsome assassin but now values peace, often lamenting how his comrades forget his existence. The initial dynamic of attempted conquest is further complicated by the arrival of Angol Mois, a powerful but childlike being who reveres Keroro and is destined to destroy the planet, though she mostly just wants to help.

While the series is largely episodic, featuring the platoon's failed attempts to take over the world through elaborate schemes that always backfire, there are several notable narrative arcs that provide more dramatic tension. One of the most significant is the Garuru Platoon arc, where Keroro's older brother, Garuru, arrives to evaluate the mission. This storyline shifts the tone to a more serious conflict, forcing the main characters to defend Earth from a far more competent and ruthless invading force. Other arcs often involve Kururu's dangerous inventions spiraling out of control, rival alien species like the Viper clan attempting to interfere, or journeys to other planets that explore the vastness of the Kerorian universe. Throughout these adventures, the series maintains a core theme of unlikely friendship between the aliens and the humans, turning a story about world conquest into a comedic slice-of-life about found family and cultural exchange.