Vitamin D has been suggested as a protective compound for diabetes mellitus. Several mechanisms linking Vitamin D to the regulation of the immune response support a role for Vitamin D in the pathogenesis of autoimmune diabetes. Epidemiological evidence and observational studies suggesting that adequate Vitamin D status is related to decreased risk of developing type 1 diabetes further corroborates this concept. However, only few and mostly underpowered randomized clinical trials have been conducted to test the effectiveness of Vitamin D supplementation in autoimmune diabetes, with disappointing results. Similarly, recent evidence linking Vitamin D action to insulin secretion and sensitivity led to the hypothesis that this compound may play a key role in the regulation of glucose homeostasis in both pre-diabetes and overt type 2 diabetes (T2D). However, the main clinical trials evaluating the efficacy of Vitamin D supplementation for the control of glucose homeostasis in people at risk for or affected by T2D have yielded inconsistent results. The aim of this review is to summarize the rationale and results of randomized clinical trials testing Vitamin D and its analogs in both autoimmune and T2D. © 2018 S. Karger AG, Basel.