Chronic infectious disease process of leprosy caused by the intracellular parasitic pathogen Mycobacterium leprae involves accumulation of highly reactive oxygen species (ROS). The present treatment method available for leprosy is MDT (Multi Drug Therapy) involves combination of Rifampicin, Dapsone and Clofazimine, although MDT disinfect leprosy patients, it has limited impact on the increased ROS production and decreased antioxidant status in affected individuals. In the present study we have investigated the causative bacillary load, lipid peroxidation, DNA damage in single cells using single cell gel electrophoresis (alkaline comet assay), oxidative stress indices in multi bacillary leprosy patients. The mean values plasma lipid peroxidation, erythrocyte oxidative stress indices in untreated leprosy cases were higher than the controls, this further increases significantly (p<0.05) with MDT. Upon supplementation with 400 IU antioxidant vitamin E we noticed a significant decrease was noticed in plasma lipid peroxidation, oxidative stress indices, and DNA damage. Hence we conclude that MDT along with vitamin E supplementation reduces the oxidative stress mediated insult to cells and bio-molecules during the chronic course of treatment in leprosy.