Dipeptidyl peptidase IV (DPP-IV), exerts several physiological functions. It regulates immune system, inflammatory response and particularly manages blood sugar levels through degradation of incretins glucagon-like peptide-1 (GLP-1) and gastric inhibitory peptide (GIP). The DPP-IV inhibitors terminate the action of DPP-IV to control the degradation of GLP-1 and GIP and increase insulin sensitivity. However, the adverse effects of DPP-IV limit its clinical applications for diabetics especially with comorbid conditions. This firmly demands novel DPP-IV inhibitors from synthetic or natural sources like herbs, plants having lesser side effects for clinical benefits. Surfacing researches provide evidences that phytochemicals from plant sources improve glucose metabolism by increasing insulin sensitivity, stimulation of pancreatic β-cells through signalling pathways like cAMP/PKA, P13K/Akt, SIRT-1, AMPK etc. The plant based compounds also improve metabolic diseases by improving insulin sensitivity in peripheral tissues. This review attempts to assimilate the data regarding capacity of natural compounds that target DPP-IV for various physiological benefits including diabetes.