ackground Stigmasterol, a naturally occurring phytoestrogen has been reported to possess many pharmacological activities. The aim of the present study was to screen the effect of stigmasterol against ketamine-induced mice model of psychosis. Methods The behavioural studies included an assessment of locomotor activity, stereotypic behaviours, immobility duration, step down latency and effects on catalepsy. Biochemical estimations involved the estimations of GABA, dopamine, GSH, MDA, TNF-?, total protein content and AChE activity. Histopathological changes and effect on androgenic parameters were also evaluated. Results Stigmasterol treated animals showed significant decrease in locomotor activity, stereotypic behaviours, immobility duration and increased step down latency. Biochemical estimations revealed increased GABA, GSH levels and decreased dopamine, MDA, TNF-? levels and AChE activity. These findings were confirmed by histopathological changes in the cortex part of the brain. Further, stigmasterol was not found to cause catalepsy and any adverse effect on the reproductive system. Conclusion This study concluded that stigmasterol could ameliorate ketamine-induced behavioral, biochemical and histopathological alterations in mice showing its potential effects in the management of psychotic symptoms.