"Squid Girl" centers around a young, anthropomorphic squid who emerges from the ocean with the intent to invade and conquer humanity as retribution for the pollution of the seas. Calling herself "Ika Musume" (literally "Squid Girl"), she arrives at a beachside restaurant called the Lemon Beach House, run by the Aizawa siblings, Chizuru and Takeru. Despite her grand ambitions, Ika Musume quickly finds herself outmatched by the mundane challenges of human life. After accidentally damaging the restaurant, she is forced to work there to repay her debt, marking the beginning of her comedic misadventures.

The series unfolds as a slice-of-life comedy, with Ika Musume attempting to adapt to human society while occasionally revisiting her original goal of world domination. Her interactions with the Aizawa siblings and other recurring characters, such as the energetic Eiko, the stoic Goro, and the mischievous Cindy, form the core of the narrative. Ika Musume's naivety and overconfidence often lead to humorous situations, as her plans frequently backfire or are derailed by her growing attachment to the people around her.

Throughout the series, Ika Musume's character evolves from a self-proclaimed invader to a more integrated member of the Lemon Beach House community. Her squid-like abilities, such as extending her tentacles and producing ink, are frequently used for comedic effect, often causing chaos or solving problems in unexpected ways. Despite her occasional attempts to assert her dominance, she is consistently portrayed as endearing and well-meaning, even as her schemes fail.

The episodic structure of the series allows for a variety of comedic scenarios, ranging from Ika Musume's attempts to understand human technology to her participation in local events and competitions. The humor often stems from the contrast between her alien perspective and the everyday lives of the human characters. While the overarching plot remains lighthearted, the series occasionally touches on themes of environmentalism, subtly reflecting Ika Musume's original motivation for invading the surface world.

The main cast is characterized by their distinct personalities and dynamics. Chizuru, the older Aizawa sibling, is strict and often exasperated by Ika Musume's antics but ultimately cares for her. Takeru, the younger sibling, is more laid-back and frequently engages in playful banter with Ika Musume. Eiko, a regular customer and friend, is enthusiastic and supportive, often encouraging Ika Musume's endeavors despite their inevitable failure. Goro, a local diver, provides a grounded counterpoint to the chaos, while Cindy, a rival of sorts, adds an extra layer of mischief to the story.

Overall, "Squid Girl" presents a lighthearted and humorous exploration of an alien-like character navigating human society, blending slapstick comedy with moments of warmth and camaraderie. The series maintains a consistent tone of playful absurdity, making it an accessible and entertaining watch for fans of comedic anime.