Social animals interact with conspecifics cooperatively and competitively for reproduction and survival. Social interaction between two individuals generally initiates with an appetitive phase that reflects interest in peers, followed by a consummatory phase that expresses a variety of goal-directed social behaviors. The insular cortex, which is located deep within the lateral sulcus in humans and on the lateral aspect of the neocortex in rodents, participates in various complex brain functions, including social function, but their cellular bases need to be fully elucidated. Using microendoscopic calcium imaging of the agranular insular cortex (AI) in mice freely interacting with social targets, we identified two subpopulations of AI neurons—“Social-ON” cells and “Social-OFF” cells—that alter their activity in opposing directions during social investigation. Social-ON cells involved those that represented social investigation independent of location and consisted of multiple subsets, each of which was preferentially active during interaction with a particular target of physical contact or under a particular behavioral state. These results unveil a novel function of AI neurons that may act to monitor the ongoing status of social exploration while an animal interacts with unfamiliar conspecifics.