Background: Tobacco causes the generation of free radicals and reactive oxygen species (ROS) which are responsible for the high rate of lipid peroxidation. Malondialdehyde (MDA) is the most widely used agent to estimate the extent of lipid peroxidation. Timely diagnosis of the condition followed by supplementation with antioxidants like beta-carotene, pro-vitamin A, vitamin A, vitamin C, vitamin E, lipoic acid, zinc, selenium, and spirulina can prevent potentially malignant disorders. Materials and Methods: In this study, serum MDA was measured according to the method of Buege, in 15 normal samples and 15 patients who were histopathologically diagnosed with potentially malignant disordered and they were prescribed with antioxidants for a period of 4 week-time following which potentially malignant patients serum MDA was analyzed again to determine the extent of peroxidation reactions. Results: The mean serum MDA level in Group C1 was 0.7900 ± 0.2336 μM/L were as the mean serum MDA level of Group S1 was 2.478 ± 0.50756 μM/L and the values between them were highly significant. The values between C1 and S2 were found to be statistically significant. The mean serum MDA of S2 was 2.160 ± 0.41252 μM/L and the values were significant when compared to S1. Conclusion: Serum MDA estimation in oral pre-cancer would serve in determining the extent of lipid peroxidation. Diagnosis of patients and administration of antioxidants has proven to be effective in declining the ROS and thus reducing the extent of damage on the cells. MDA may serve as a diagnostic tool in the estimation of oral pre-cancer and in evaluation of post-treated cases.