Abstract: Type 2 diabetes, a glucose and lipid metabolism disorder accompanied by chronic multiple organ damage, has become a huge threat to human health. α/β hydrolase domain-6(ABHD6)regulates the insulin release negatively by hydrolyzing monoacylglycerol. Small molecule ABHD6 inhibitors have been proven to lower blood-glucose and regulates energy homeostasis, which is a potential candidate for the treatment of type 2 diabetes. This paper introduced the ABHD6 signaling pathway and its mechanism, then reviewed the progress of small molecule ABHD6 inhibitors with different structures in recent years, and analyzed the structure activity relationship.