Both peripheral and autonomic neuropathies are characterized by a progressive loss of nerve fiber function. Most peripheral neuropathy affects the extremities, particularly the lower legs and the feet, but also the hands, whereas damage to the autonomic nervous system may lead to imbalances between the sympathetic and parasympathetic nerve fibers that innervate the heart and blood vessels, as well as abnormalities in heart rate control and vascular dynamics. To prescribe or engage in exercise that is both safe and effective, health care providers and patients with diabetes mellitus need to increase their understanding of the pathophysiological nature of neuropathies and the physical activity hurdles that may arise from the presence of a neuropathy. With proper care and preventative measures, patients with diabetes mellitus that experience either type of neuropathy can benefit from regular participation in mild to moderate aerobic, resistance, and balance activities, assuming they take any potential alterations into account to ensure that exercise is safe and effective.