"Kiddy Girl-AND" is a 26-episode anime series set in the distant future, where humanity has expanded into space and established the Galactic Organization of Trade and Administration (GOTT). The organization oversees interstellar trade and maintains peace across the galaxy. The story centers on two young agents, Éclair and Lumiere, who work for GOTT's ES (Encounter of Shadow-work) branch, tasked with investigating and resolving various incidents that threaten galactic stability.

Éclair, a cheerful and energetic girl, and Lumiere, a calm and analytical counterpart, form a contrasting yet complementary duo. Their partnership is tested as they take on missions ranging from uncovering smuggling operations to confronting rogue entities that disrupt the balance of power. The narrative explores their growth as agents and individuals, delving into their personal struggles and the evolving dynamics of their relationship.

The series introduces a broader conflict involving a mysterious force known as the "Crimson Blade," which seeks to destabilize the galaxy. As Éclair and Lumiere investigate, they uncover deeper conspiracies within GOTT itself, revealing internal corruption and hidden agendas. The plot intertwines action, mystery, and moments of lighthearted humor, balancing episodic missions with an overarching storyline.

Supporting characters include Ascoeur, a high-ranking GOTT official who mentors the protagonists, and Q-feuille and Q-lisch, two young girls with a mysterious connection to the series' central conflict. The narrative also revisits characters from the prequel series, "Kiddy Grade," providing continuity for fans while introducing new elements to expand the universe.

Themes of trust, loyalty, and the pursuit of justice are central to the story, as Éclair and Lumiere navigate the complexities of their roles and the moral ambiguities of their missions. The series concludes with a resolution to the immediate threats, though it leaves room for further exploration of the galaxy's vast and intricate political landscape.