Abstract: Oxidative stress is the outcome of an imbalance between the production and neutralization of reactive oxygen and nitrogen species (RONS) such that the antioxidant capacity of cell is overwhelmed. The present review briefly summarized the underlying role of overwhelming levels of RONS in the pathophysiology of diabetes mellitus (DM). The review is based on using keywords to obtain information from publications in PubMed, ScienceDirect and Google Scholar from 1970-2015. The primary causative factor of oxidative stress in DM is hyperglycemia, which operates via several mechanisms. However, the individual contribution of other intermediary factors to hyperoxidative stress remains undefined, in terms of the dose response relationship between hyperglycemia and overall oxidative stress in DM. Intuitively, the inhibition and/or scavenging of intracellular free radical formation provide a therapeutic strategy to prevent oxidative stress and ensuing pathologic conditions. The integration of antioxidants formulations into conventional therapeutic interventions, either by ingestion of natural antioxidants or through dietary supplementation should be encouraged for a holistic approach to the management and prevention of DM and complications associated with the pathology.