Gliptins, commonly known as clinical DPP-IV inhibitors have become a new class of potential drug candidate and are being hoped as a permanent eraser for type 2 diabetes. Therefore, gliptins have been a centre of research and development. As a result of the efforts made towards developing effective gliptins, the first clinical proof of concept for efficacy was confirmed in 1998 when NVP-DPP728 came into focus. Thus, from 1998 to 2014, these 17-years of the heightened research towards drug discovery has resulted in seventeen gliptins. Among these, eight gliptins are currently approved and in clinical usages for type 2 diabetes therapies, while others are in different stages of clinical trials. This review covers the various approaches and methodologies used in the syntheses of only those DPP-IV inhibitors in clinical uses having suffix gliptin. In addition, it also encompasses their biological activity and their binding interactions in the active site of DPP-IV that are responsible for their drug candidacy.