"Bottom Biting Bug" is a comedic anime series centered around the misadventures of a group of high school students who become entangled in a bizarre phenomenon involving a mysterious insect. The titular "Bottom Biting Bug" is a rare creature that, when it bites someone, causes uncontrollable laughter and erratic behavior. The story unfolds as the bug infiltrates the school, leading to a series of chaotic and humorous situations.

The protagonist, Haruto, is an ordinary high school student with a knack for getting into trouble. Alongside his best friend, Yuki, a pragmatic and level-headed classmate, Haruto attempts to uncover the source of the bug's appearance. Their investigation leads them to the school's eccentric biology teacher, Dr. Tanaka, who reveals that the bug is a result of a failed experiment gone awry. As the bug spreads its influence, the students must work together to contain the outbreak while navigating the increasingly absurd consequences of its bites.

Key characters include Rina, a popular and confident student who becomes a reluctant ally in the quest to stop the bug, and Taro, a shy and introverted classmate whose unexpected bravery plays a pivotal role in the group's efforts. The series balances slapstick humor with moments of camaraderie, as the students learn to rely on each other despite their differences.

The plot escalates as the bug's effects grow more severe, culminating in a school-wide crisis during the annual cultural festival. The students devise a plan to lure the bug into a trap, using their unique skills and teamwork to outsmart the creature. The resolution ties together the comedic and heartfelt elements of the story, highlighting the growth of the characters and their ability to overcome challenges together.