Type 1 diabetes (T1D) is a T-cell-mediated autoimmune disease resulting in islet β-cell destruction, hypoinsulinaemia and severely altered glucose homeostasis. Although the mechanisms that initiate T1D still remain elusive, a breakdown of immune tolerance between effector T-cells (Teff) and regulatory T-cells (Treg) is considered to be the crucial component leading to autoimmunity. As such, strategies have been developed to boost the number and/or function of Tregin the hope of specifically hampering the pathogenic Teffactivity. In this review, we will summarize the current understanding of biomarkers and functions of both forkhead box protein 3 (FoxP3)+Tregand type 1 regulatory T (Tr1) cells in health and in T1D, examine the outcome of experimental therapies in both animal models and humans via manipulation of Tregresponses and also provide an outlook on the potential of Treg-based immunotherapies in the prevention and treatment of this disease. Discussed immunotherapies include adoptive transfer of ex-vivo expanded FoxP3+Treg, manipulation of Tregcells via the interleukin (IL)-2/IL-2R pathway and induction of Tregby tolerogenic peptides, tolerogenic dendritic cells or altered gut microbiota.