"Mao-chan" is a 26-episode anime series that blends comedy, science fiction, and slice-of-life elements. The story centers on Mao Onigawara, a cheerful and determined elementary school girl who is also the granddaughter of Japan's Ground Defense Force commander. In a world where Japan faces frequent attacks by mysterious alien creatures known as "Foreigners," the government establishes the "Earth Defense Force" to combat these threats. However, the public grows weary of military intervention, leading to the creation of a more approachable and less intimidating defense unit: the "Cute Defense Club."

Mao, along with her friends Misora Tsukishima and Sylvia Maruyama, forms the core of this club. Each girl represents a branch of Japan's defense forces—Mao for the Ground Defense Force, Misora for the Air Defense Force, and Sylvia for the Maritime Defense Force. Despite their young age and lack of formal training, the trio is tasked with protecting Japan from the whimsical and often bizarre Foreigners. These creatures range from giant floating heads to mischievous entities that disrupt daily life, but they are more comical than menacing. The girls use unconventional and childlike methods to neutralize the threats, often relying on their unique personalities and teamwork rather than traditional military tactics.

Mao is the energetic and optimistic leader, Misora is calm and analytical, while Sylvia, a half-Japanese, half-American girl, brings a playful and carefree attitude. Their missions frequently involve creative problem-solving, such as using toys, games, or even food to outsmart the Foreigners. The series balances lighthearted humor with moments of camaraderie and growth, as the girls navigate their responsibilities while maintaining their innocence and joy as children.

The narrative structure is episodic, with each episode presenting a new Foreigner threat and the Cute Defense Club's efforts to resolve it. While the series primarily focuses on comedy and the girls' adventures, it occasionally touches on themes of friendship, responsibility, and the importance of finding non-violent solutions to conflicts. The tone remains consistently light, making it accessible to a younger audience while still offering charm and entertainment for older viewers.