It has recently been estimated by the American Diabetes Association that 21 million Americans, or about 7% of the U.S. population, have diabetes, while an additional 54 million Americans have pre-diabetes. The onset and progression of these disorders and related complications are linked to impairments in glucose and lipid metabolism, both of which are associated with increased production of reactive oxygen and nitrogen species (RONS). Increased RONS production coupled with impaired antioxidant defense (a common finding among patients with diabetes) promotes oxidation of specific biomolecules (lipid, protein, DNA), which can lead to an exacerbation of diabetic complications. While bloodborne variables related to these disorders have traditionally been measured in a fasted state, increasing evidence suggests that measurement of postprandial glycemia, lipemia, and oxidative stress may provide more important clinical information concerning an individuals susceptibility to diabetes onset and disease progression. While drugs to treat hyperglycemia and hyperlipidemia have been reported in some studies to promote favorable outcomes related to attenuating the postprandial rise in blood glucose and triglycerides, one non-pharmaceutical approach which may have promise is the performance of regular exercise. Both acute and chronic exercise may aid in attenuating postprandial oxidative stress in three distinct ways. First, exercise stimulates an increase in endogenous antioxidant enzyme activity. Second, exercise improves blood glucose clearance via enhanced GLUT 4 translocation and protein content, as well as enhanced insulin-insulin receptor binding and post-receptor signaling. Third, exercise improves blood triglyceride clearance via a reduced chylomicron- triglyceride half-life and enhanced lipoprotein lipase activity. In this article we provide evidence for the potential role of exercise in modulating postprandial oxidative stress in diabetic and pre-diabetic individuals. It is certainly possible that exercise may prove beneficial in this regard. If so, and in accordance with the recent joint initiative of the American College of Sports Medicine and the American Medical Association, exercise may be viewed as “medicine” for individuals who are at increased risk for postprandial oxidative stress.