Marijuana derived from the plant Cannabis sativa has been used for the treatment of many gastrointestinal (GI) disorders, including anorexia, emesis, abdominal pain, diarrhea, and others. However, its psychotropic side effects have often limited its use. Several cannabinoid receptors, which include the cannabinoid receptor 1 (CB1), CB2, and possibly GPR55, have been identified throughout the GI tract. These receptors may play a role in the regulation of food intake, nausea and emesis, gastric secretion and gastroprotection, GI motility, ion transport, visceral sensation, intestinal inflammation, and cell proliferation in the gut. However, the regulation of nausea and vomiting by cannabinoids and the endocannabinoid system has shed new knowledge in this field. Thus far, despite evidence of visceral sensitivity inhibition in animal models, data in irritable bowel syndrome (IBS) patients is scarce and not supportive. Furthermore, many compounds that either act directly at the receptor or increase (or reduce) ligand availability have the potential to affect other brain functions and cause side effects. Novel drug targets such as FAAH and monoacylglycerol lipase (MAGL) inhibitors appear to be promising in animal models, but more studies are necessary to prove their efficiency. The promise of emerging drugs that are more selective and peripherally acting suggest that, in the near future, cannabinoids will play a major role in managing an array of GI diseases.