The gut contains one of the largest stem cell populations in the body, yet has been largely overlooked as a source of potentially therapeutic cells. The stem cells reside in the crypts located at the base of the protruding villi, reproduce themselves, and repopulate the gut lining as differentiated cells are sloughed off into the lumen. Some studies have demonstrated that gut stem cells can be isolated and maintained in culture, but the field is currently hampered by the lack of clear markers for these cells. Nevertheless, the relative accessibility of the cells and the similar pathways of differentiation of both intestinal and pancreatic endocrine cells make the gut an attractive potential source of cells to treat diabetes. In particular, it may be possible to recapitulate islet development by the introduction of specific factors to gut stem cells. Alternatively, gut endocrine cells might be coaxed to produce insulin and secrete it into the blood in a meal-responsive manner. Several investigations support the feasibility of both approaches as novel potential therapies for diabetes. Utilizing a patient's own gut cells to re-establish endogenous meal-regulated insulin secretion could represent an attractive approach to ultimately cure diabetes.