Multiple organs work together to achieve a balance between glucose entry into blood circulation (from the liver, glucose is absorbed through intestinal mucosa after meals) and peripheral tissue glucose uptake (mainly brain and skeletal muscles). Blood glucose is controlled and maintained within a narrow range under normal physiological conditions, which is referred to as glucose homeostasis. Endogenous insulin is secreted when blood glucose levels rise. Its release can be aided by other factors such as amino acids and hormones released from the gut following food consumption, a phenomenon known as the incretin effect. Diabetes mellitus is caused by defects in insulin secretion, insulin action, or both, resulting in chronic hyperglycemia caused by disturbed carbohydrate, fat, and protein metabolism. The current review discusses the role of incretin-based therapies in the management of diabetes mellitus and the maintenance of glucose homeostasis.