The most common cause of ischemic colitis (IC) is a sudden and transient reduction in splanchnic perfusion. In the younger population, medications are an increasingly recognized cause of ischemic bowel disease. Over-the-counter supplements may also lead to the development of ischemic colitis through similar effects. We present a case of ischemic colitis in a 42-year-old active duty service member after using the performance-enhancing supplement, NO-Xplode. In this report, we review the pharmacology of this supplement and its proposed mechanism of injury.