Invariant natural killer T (iNKT) cells are CD1d-restricted T cells with regulatory functions. iNKT cells are numerically and functionally deficient in experimental models of type 1 diabetes mellitus (T1DM). Moreover, various experimental strategies correcting the defect of or stimulating iNKT cells prevent T1DM. Here, we review the data on the role of iNKT cells in the development of T1DM and discuss indications, obstacles and prospects of the use of iNKT cell manipulations in the prevention and treatment of human T1DM.