Type 2 diabetes mellitus and its precursor, insulin resistance, are metabolic disease states characterized by impaired regulation in the delivery, transport, and/or storage of energy substrates (primarily carbohydrate- and fat-based fuels). A hallmark feature of patients with type 2 diabetes is prolonged periods of hyperglycemia due to a decreased responsiveness of metabolically active peripheral tissues to the actions of insulin (i.e., metabolic inflexibility). Accordingly, efforts to modify skeletal muscle substrate handling in type 2 diabetes patients so that the capacity for fat oxidation and metabolic flexibility is improved should be a primary goal for the treatment of these disorders. Two potent interventions for improving whole-body glucose homeostasis are exercise and diet. A single bout of either resistance or endurance exercise reduces the prevalence and duration of hyperglycemic excursions in patients with type 2 diabetes, an effect lasting well into the next day. With regard to diet, the carbohydrate content of a meal and the glycemic index (GI) of the carbohydrate consumed are both major determinants of the postprandial glycemic response. Diets containing high-GI carbohydrates have been shown to be independent risk factors for type 2 diabetes onset, while in obese insulin-resistant individuals, low-GI diets are effective for inducing both weight loss and improving insulin action and glucose tolerance. The implementation of physical activity and dietary modifications are effective low-cost treatment options for controlling hyperglycemic episodes in patients with type 2 diabetes.