The ultimate aim of the present study was to exploring the chemopreventive efficacy of diosgenin on 7,12-dimethylbenz(a)anthracene (DMBA) induced hamster buccal pouch carcinogenesis. The chemopreventive potential of diosgenin was evaluated by measuring the tumour incidence, tumour volume and tumour burden as well as analyzing the activities of detoxification agents, levels of lipid peroxidation byproducts and antioxidants status by specific colorimetric methods. Oral squamous cell carcinoma (OSCC) was developed in the buccal pouches of male Syrian golden hamsters by painting with 0.5% DMBA in liquid paraffin, thrice a week for 16 weeks. DMBA painted animals were indicating the morphological changes as depicted as hyperplasia, dysplasia and well-developed squamous cell carcinoma. Moreover, antioxidants and lipid peroxidation byproducts levels were drastically altered in DMBA painted hamsters. Oral administration of diosgenin (80 mg/kg bw) to DMBA painted hamsters on alternate days for 16 weeks significantly reduced the formation of oral tumour and normalized the above biochemical abnormalities. We conclude that the diosgenin is probably potent chemopreventive agent due to their antioxidant function in DMBA induced hamster buccal pouch carcinogenesis.