Cytotoxic effect of tobacco both in vivo and in vitro is confirmed by a wealth of scientific evidences available in literature. It is established that smokeless tobacco related tissue damage is related to reactive oxygen species production in oral cells, peritoneal macrophages, hepatic mitochondria and microsomes. In the present study, it is explored to compare the cytotoxic effects of three different tobacco samples and cyto-protective effects of three different plant extracts. Cyto-toxicity induced by tobacco samples andcyto-protective effects of plant extracts, when analysed, a reduction in % cell viability of oral epithelial cells after incubating with different tobacco extract was noted in a concentration dependent manner. Viability noted with tobacco -1 exposure was 73-52 % with increasing concentration, with tobacco -2 was 75 to 32% and with tobacco-3 was 52 to 23%. Simultaneous treatment with plant extracts along with tobacco samples resulted in reduction in cytotoxic effect reflected as increase in % viability than tobacco treatment alone, indicating the cyto-protective effect of plant extracts, but not to the level of untreated controls.