In the year 20XX, the world is suddenly attacked by a mysterious and overwhelming force known as void, a toxic new lifeform that threatens the survival of humanity. The only beings capable of resisting these creatures are the toxients, colloquially referred to as poison men, who possess harmful toxins within their own bodies. The story follows these toxients as they are deployed on missions to eliminate the void and protect the human race.

The setting is a near-future world where humanity relies on these dangerous yet indispensable individuals. The narrative centers on the Tokyo branch of the organization that manages the toxients, a facility led by a branch chief named Akasaka, whose task is to supervise and deploy these unique assets. Recognizing that the toxients suffer from a public image problem due to their poisonous nature, the Tokyo branch initiates a public relations campaign, producing videos to boost their popularity and improve their standing with the people they protect.

The main characters are the toxients themselves, each identified by a management number and possessing distinct personalities. The roster includes An, the group's comforting presence; Hemlock, a lover of books and difficult problems; Cyan, who has a sharp and irritable temperament; Argot, a pacifist who loves peace; Dion, who is prone to becoming a drunkard; C.B., who stands out due to his tentacles; Chain, who loves anything amusing; and a supporter named Suzaku, who acts as the branch chief's right-hand man.

Toxic-a-Holic Alternate Episode is an action fantasy manga that operates on the principle of fighting poison with poison. The narrative arcs revolve around the dual life of the toxients: their intense battle missions against the enigmatic and non-communicative void, and their daily struggles with public perception and personal relationships within the organization. The series explores themes of duty, isolation, and the quest for acceptance in a society that both needs and fears its protectors.