Glucagon-like peptide-1 and Glucose-dependent insulinotropic polypeptides are the most investigated gut peptides concerned with the biological glucose milieu. Early and late metabolism of incretin governs glucose homeostasis in diabetes mellitus. Dipeptidyl Peptidase-4, present in pancreatic alpha cells, is responsible for incretin degradation. Emerging biotechnological and molecular approaches established the pathophysiological role of Dipeptidyl Peptidase-4 and incretin in type 2 diabetes mellitus. Thus, various conventional synthetic Dipeptidyl Peptidase-4 inhibitors have been formulated, but they have serious adverse effects such as cancer, pancreatitis, cardiovascular risks, hepatic dysfunctions, etc. So, the concoction of a Dipeptidyl Peptidase-4 inhibitor entity with less or no severe adverse event becomes a need for society and medical corridor. Over the last two decades, natural or conventional herbal remedies have emerged as an alternate therapy for diabetes and treating its complications. This review summarized various plants (Emblica officinalis, Adenia viridiflora, Cleome droserifolia, Lens culinaris, Hedera nepalensis Melicope glabra, etc.) Dipeptidyl Peptidase-4 inhibitors, which have been preclinically proven for hyperglycemia treatment.