Diabetes mellitus (DM) is one of the deadliest metabolic diseases in the world, with a high mortality rate. Diabetes mellitus is characterised by insulin resistance and inadequate insulin production from pancreatic -cells, as is well known. Due to the adverse reactions of the current therapy, there is an urgent need for the development of new effective anti-diabetic pharmaceuticals, particularly alpha-amylase inhibitors with fewer side effects. In addition, natural products are well-known sources for the discovery of novel bioactive compounds which may function as scaffolds for drug discovery, including the discovery of new antidiabetic medications. Using an in silico approach, the current investigation sought to identify novel drug-like molecules as anti-diabetic compounds in Enicostemma littorale. Enicostemma littorale blume (E. littorale), a perennial herb belonging to the Gentianaceae family, is widespread in India. Observed intermolecular interactions between target proteins and various anti-diabetic compounds derived from Enicostemma littorale. Four compounds with the highest docking scores (vanillic acid, p-coumaric acid, protocatechuic acid, and hydroxybenzoic acid) were chosen for further interaction analysis based on the results of docking studies. For experimental substantiation of the antidiabetic activity of these compounds, testing is necessary.