The escalating global prevalence of diabetes, particularly type 2 diabetes, underscores the urgency of developing novel therapeutic strategies. One such approach is the inhibition of α-glucosidase, an enzyme crucial in the breakdown of carbohydrates, thus influencing postprandial blood glucose levels. This study aimed to investigate the inhibitory effect of Barteria nigritana green-synthesized zinc oxide on α-glycosidase, a key enzyme implicated in the progression of diabetes. The phytochemicals present in the compound were determined using standard procedures to achieve this aim. The chemical composition of the synthesized BNZnONPs was characterized using GC-FID analysis. Molecular interaction of all the identified compounds with a-glucosidase was appraised via the Glide XP-docking panel of Schrodinger suite v12.4, while the Adsorption, Distribution, Metabolism, Excretion, and Toxicity (ADMET) prediction of the best-fit compounds was made using the SwissADME search engine. Furthermore, in vitro analysis of the α-glucosidase inhibitory activity of B. nigritiana zinc nanoparticles was investigated using a conventional method. The GC-FID screening identified twenty compounds with highest abundance of Catechol, (+)-Pinoresinol, Pyrogallol, Picric acid, Flavanone, 2, Hydroxyl phenol, and Assculetin (50.4, 32.2, 9.3, 7.9, 7.8, and 7.0 ppm respectively) and the compounds with the low concentrations were Resveratrol, Phloroglucinol, Phenetole, Alpha naphthol and 3,4-Hydroxyl toluene (2.4, 2.0, 2.3, 2.2 and 2.2 ppm, respectively). Among the identified compounds, resveratrol, 2-hydroxylphenol, 2, 3-dihydroxylphenol, α-naphthol, and flavonones demonstrated the highest interaction with α-glucosidase, recording docking scores of -7.763, -7.025, -7.018, 6.778, and -6.714 Kcal/mol, respectively. These compounds interacted predominantly with amino acid residues within and around the α-glucosidase active site, using hydrogen bonding. The ADMET properties indicate that 2-hydroxyphenol, 3,4-hydroxyphenol, α-naphthol, and flavonones exhibit favorable drug-likeness, pharmacokinetic properties, and a good safety profile. Interestingly, the nanoparticles demonstrated a very good inhibitory action against α-glucosidase with 1C50 values of 4.22µg/mL. Thus, B. nigritina phytochemicals are promising potential targets for the treatment and development of an anti-diabetic drug.