Initially, high school students Galko, Otako, and Ojou appear to be incompatible. Galko is an outgoing party girl, but beneath her confident exterior lies a kind and virtuous heart. Contrarily, Otako is a plain-looking girl with a fondness for manga and a penchant for sarcasm. Meanwhile, Ojou is affluent and charming but prone to forgetfulness. However, despite their differences, the trio is the closest of friends. They bond over discussions about myths and frank discussions about women's anatomy. Oshiete! Galko-chan hilariously depicts the lively experiences of these contrasting personalities as they share their opinions on daily life with no inhibition towards taboo subjects or sensitive topics. Even though Galko may become bashful when discussions get too explicit!