Forkhead box O (FOXO) proteins are transcription factors that are involved in many physiological processes, including diabetes mellitus, which is a complex, multifactorial metabolic disorder. FOXO proteins are emerging as pivotal regulators in the progression of diabetes mellitus, mainly by inhibiting insulin or insulin-like growth factor, but little is known about their roles in diabetes mellitus. Although no targeted therapy exists to slow the development of diabetes and diabetes-related complications, several recent advances have clarified the molecular mechanisms underlying the disease. This review summarizes findings about FOXO proteins and diabetes mellitus, and sheds new light on the roles of FOXO proteins in diabetes mellitus.