The aim of the present study was to investigate the effect of Solanum xanthocarpum on KB human oral cancer cells by analyzing its anti-proliferative and apoptotic properties as well as its inhibitory effect on cell adhesion. In this study, the leaves extract of S. xanthocarpum was prepared using the maceration method. Cytotoxic effect of different doses of the S. xanthocarpum extract was assessed using MTT assay. Measurements of reactive oxygen species (ROS), lipid peroxidation and antioxidant enzymes were also performed. In addition, we also studied the impacts of S. xanthocarpum on the apoptosis and mitochondrial membrane potential of KB cells. Determination of antioxidant enzymes and lipid peroxidation was performed using biochemical methods. The S. xanthocarpum showed cytotoxic activity against KB cells with IC50 (200 μg/mL). Besides, DCFH-DA staining and acridine orange/ethidium bromide staining results demonstrated that S. xanthocarpum induced the generation of ROS and apoptosis in KB cells, respectively. Based on the Rh-123 staining results, S. xanthocarpum decreased mitochondrial depolarization in KB cells. Furthermore, the S. xanthocarpum treatment contributed to increased lipid peroxidation, accompanied by reduced activities of superoxide dismutase and catalase, as well as decreased glutathione content. Taken together, these findings indicate that S. xanthocarpum extract might comprise bioactive compounds of therapeutic significance, which can inhibit the growth of KB cells.