Diabetes, a chronic metabolic disorder characterised by hyperglycaemia has become a major global health concern, with an increasing prevalence worldwide (Mukhtar, Galalain & Yunusa, 2020). Despite the availability of various anti-diabetic drugs, the search for natural remedies to manage diabetes has gained significant attention. Mangifera indica extracts have been studied for their anti-oxidant, anti-diabetic, lipid-lowering and anti-obesity potentials (Kumar et al., 2021). This study was designed to investigate the therapeutic effects of Mangifera indica methanol extract against Diabetes Mellitus, using in silico methods, Molecular docking simulations were performed to assess the binding affinities and interactions of the identified compounds from the Gas Chromatography/Mass Spectometry analysis result with key enzymes, proteins and hormones involved in glucose metabolism, such as alpha-amylase, insulin receptors, Glucose Transporter type 4 and Glucagon-like peptide 1. 6-methyl-2-(3-nitrophenyl) imidazo[1,2-a] pyridine had the highest binding affinity with Insulin receptors(-7.6kcal/mol), alpha amylase(-8.0kcal/mol) and Glucose transporter type 4(-8.5kcal/mol). Oxime-, methoxy-phenyl had the highest binding affinity with Glucagon-like peptide 1(-6.5kcal/mol). These findings suggest that mango leaves could serve as a source of natural anti-diabetic agent, which could lead to the development of new and effective treatments for diabetes. Further in vitro and in vivo studies are warranted to validate the bioactivity of these compounds and their mechanisms of action. Overall, this project contributes to the growing body of evidence supporting the use of in silico approaches for the discovery of novel antidiabetic agents from natural products.