Background: Newly, chemopreventive technique might be a hopeful advancement in developing countries for treating cancers with the aid of toxic less natural-based constituents. Malignancy urges to augment effectual chemopreventive agents that are looking forward to suppressing the tumors which may be stimulated by chewing and smoking of tobacco and over alcohol consumption related to the high prevalence of human oral cancer (OC) patients. Materials and Methods: In the present research, we examined to assess antioxidants, lipid peroxidation (LPO), and detoxification enzymes levels of anticancer activity of mangiferin on 0.5% 7,12-dimethylbenz[a]anthracene (DMBA) provoked hamster cheek pouch carcinoma. OC on hamster buccal pouch (HBP) was incited by DMBA treatment for thrice per week for over 14 weeks. Results: About 100% well-defined OC establishment with body weight (b.wt), tumor burden, antioxidant, LPO and liver marker enzymes, and also histological changes were observed on DMBA-challenged buccal pouch carcinoma (BPC) in hamsters. Orally treated mangiferin at an effective dosage of 50 mg/kg b.wt, to DMBA painted hamsters were significantly averted the b.wt, succession of tumor, the biochemical as well as histopathological changes. Conclusion: The findings of this work clearly suggest that the anti-carcinoma effect of mangiferin possess the modulatory effects on potent antioxidant, anti-LPO, and detoxification agents to expel the metabolites of malignant cells, on DMBA-provoked BPC in hamsters.