The digestion and absorption of nutrients, and the neuroendocrine signals arising from their interaction with the gut, are fundamental to the regulation of energy intake and blood glucose. Sweet taste receptors, responding to a broad array of sugars and artificial sweeteners, are found not only on the tongue but also in the small intestine. They play a role in the release of gut peptides in response to sugars, and regulate the expression of intestinal glucose transporters. Epidemiological evidence suggests that consumption of artificial sweeteners, as well as sugars, increases the risk of developing type 2 diabetes; the underlying mechanisms are unclear, but could involve the gut. Recent studies investigating the expression and regulation of intestinal sweet taste receptors and glucose transporters in diabetes and obesity are yielding insights into the pathophysiology of these disorders.