Prolonged hyperglycemia is toxic to pancreatic β cells, generating excessive reactive oxygen species, defective glucose-stimulated insulin secretion, decreased insulin production, and eventually β cell death and diabetes. Nrf2 is a master regulator of cellular responses to counteract dangerous levels of oxidative stress. Maintenance of β cell mass depends on Nrf2 to promote the survival, function, and proliferation of β cells. Indeed, Nrf2 activation decreases inflammation, increases insulin sensitivity, reduces body weight, and preserves β cell mass. Therefore, numerous pharmacological activators of Nrf2 are being tested in clinical trials for the treatment of diabetes and diabetic complications. Modulating Nrf2 activity in β cells is a promising therapeutic approach for the treatment of diabetes. Development of type 2 diabetes is accompanied by a chronic increase of oxidative stress in β cells, which results in oxidative damage and reduced functional β cell mass. The Nrf2 antioxidant system is crucial for controlling functional β cell mass by maintaining β cell redox balance, increasing β cell survival, preserving β cell function, and promoting β cell proliferation. A large number of natural antioxidant compounds stimulate the Nrf2 pathway. Several related compounds are under investigation for their efficacy as treatments for diabetes in clinical trials. Manipulation of the Nrf2 antioxidant pathway is a promising future therapeutic avenue for the treatment of both types of diabetes. [ABSTRACT FROM AUTHOR]