AbstractSchizophrenia is a chronic brain disorder characterized by positive symptoms (delusions or hallucinations), negative symptoms (impaired motivation or social withdrawal), and cognitive impairment. In the present study, we explored whether D‐pinitol could ameliorate schizophrenia‐like behaviors induced by MK‐801, an N‐methyl‐D‐aspartate receptor antagonist. Acoustic startle response test was conducted to evaluate the effects of D‐pinitol on sensorimotor gating function. Social interaction and novel object recognition tests were employed to measure the impact of D‐pinitol on social behavior and cognitive function, respectively. Additionally, we examined whether D‐pinitol affects motor coordination. Western blotting was conducted to investigate the mechanism of action of D‐pinitol. Single administration of D‐pinitol at 30, 100, or 300 mg/kg improved the sensorimotor gating deficit induced by MK801 in the acoustic startle response test. D‐Pinitol also reversed social behavior deficits and cognitive impairments induced by MK‐801 without causing any motor coordination deficits. Furthermore, D‐pinitol reversed increased expression levels of pNF‐kB induced by MK‐801 treatment and consequently increased expression levels of TNF‐α and IL‐6 in the prefrontal cortex. These results suggest that D‐pinitol could be a potential candidate for treating sensorimotor gating deficits and cognitive impairment observed in schizophrenia by down‐regulating transcription factor NF‐κB and pro‐inflammatory cytokines in the prefrontal cortex.