Diabetes mellitus (DM) is a metabolic disorder that remains a major health problem in the world. It is characterized by relative or absolute deficiency of insulin secretion and/or insulin resistance that causes chronic hyperglycemia and impaired carbohydrates, lipids, and proteins metabolism. Diabetes has been known as an oxidative stress disorder caused by imbalance between free radical formation and the ability of the body's natural antioxidants. Many studies have suggested that oxidative stress play a role in systemic inflammation, endothelial dysfunction, impaired secretion of pancreatic cells and impaired glucose utilization in peripheral tissues. In patients with type 2 diabetes mellitus (T2DM) who are at risk, intensive intervention with multiple drug combinations and lifestyle modifications showed a beneficial effect on vascular complications and reduce mortality rate due to cardiovascular disease and other causes. There has also been shown that neutralization of reactive molecules can significantly inhibit the development of endothelial dysfunction, cardiomyopathy, retinopathy, nephropathy, and neuropathy in patients with DM. Recently the use of antioxidants still remains a controversy, but its use as a therapy for DM can be considered because its demonstrated effectiveness in lowering the risk of developing diabetes and its complications. Various antioxidants have been developed for oxidative stress treatment in DM, including the use of vitamins and supplements as well as the use of some components of plants and fresh fruits which have demonstrated antioxidant effect in DM patients. In some recent studies, some drugs routinely used in the treatment of DM also demonstrated antioxidant effects.