"Mushibugyō" is set in an alternate version of Edo-period Japan, where giant insects known as "Mushi" threaten humanity. To combat this menace, the Tokugawa shogunate establishes the Insect Magistrate Office, a specialized force tasked with exterminating these creatures and protecting the populace. The story centers on Jinbei Tsukishima, a young and earnest swordsman who arrives in Edo to fulfill his father's dying wish: to serve as a Mushibugyō, one of the elite warriors tasked with defending the city.

Jinbei's journey begins when he encounters the Insect Magistrate Office, led by the stoic and skilled Mugai. Mugai recognizes Jinbei's potential and allows him to join the team, which includes a diverse group of fighters, each with unique abilities and personalities. Among them are Hibachi, a fiery and determined warrior; Tenma, a calm and analytical strategist; and Oharu, a cheerful and resourceful girl who provides support. Together, they face increasingly dangerous Mushi, uncovering the origins of these creatures and the dark forces behind their emergence.

As the story progresses, Jinbei's growth as a warrior and leader becomes a central focus. His unwavering determination and sense of justice inspire those around him, even as he grapples with his own insecurities and the weight of his responsibilities. The narrative delves into the complexities of the Mushi threat, revealing that their existence is tied to a deeper conspiracy involving powerful factions within the shogunate and beyond. The Insect Magistrate Office must navigate political intrigue, betrayal, and personal conflicts while battling the ever-evolving Mushi.

The series balances action-packed battles with character-driven moments, exploring themes of duty, camaraderie, and the struggle to protect what matters most. Jinbei's relationships with his comrades evolve, highlighting their shared resolve and individual growth. The stakes escalate as the true nature of the Mushi is unveiled, culminating in a climactic confrontation that tests the limits of the Insect Magistrate Office and their commitment to safeguarding humanity. Through its blend of historical fantasy and intense storytelling, "Mushibugyō" offers a compelling tale of heroism and perseverance in the face of overwhelming odds.