Selenium (Se) is a micronutrient essential to human health, the function of which is mediated in part by incorporation into a class of proteins known as selenoproteins (SePs). As many SePs serve antioxidant functions, Se has long been postulated to protect against inflammation and cancer development in the gut by attenuating oxidative stress. Indeed, numerous studies over the years have correlated Se levels with incidence and severity of intestinal diseases such as inflammatory bowel disease (IBD) and colorectal cancer (CRC). Similar results have been obtained with the Se transport protein, selenoprotein P (SELENOP), which is decreased in the plasma of both IBD and CRC patients. While animal models further suggest that decreases in Se or SELENOP augment colitis and intestinal tumorigenesis, large-scale clinical trials have yet to show a protective effect in patient populations. In this review, we discuss the function of Se and SELENOP in intestinal diseases and how research into these mechanisms may impact patient treatment.