Vitamin B6 is an essential nutrient for the human health. It is involved in more that 150 metabolic reactions which regulate the metabolism of glucose, lipids, amino acids, DNA, and neurotransmitters. In addition, vitamin B6 is an antioxidant molecule able to  counteracting the formation of reactive oxygen species (ROS) and advanced glycation end-products (AGEs). Epidemiological and experimental studies indicated the reduced levels of vitamin B6 can cause diabetes. In contrast other studies show that diabetes decreases vitamin B6 levels. Thus these findings lead to envisage the existence of a vicious circle at the basis of the relationship between vitamin B6 and diabetes. This entry reports the main evidence concerning the role of vitamin B6 in diabetes and examine the underlying molecular and cellular mechanisms.