: Molecular docking analysis plays a crucial role in drug discovery and development by elucidating the interactions between drugs and target molecules. In this study, we employed molecular docking analysis to investigate the binding interactions between orientin, a well-known antidiabetic drug, and a set of genes involved in diabetes regulation. Three-dimensional models of the target proteins, including insulin receptor (IR), glycogen synthase kinase, and glucokinase, were generated using computational tools and available crystal structures. Rigorous refinement and validation techniques were applied to ensure model accuracy.Using Auto dock for molecular docking and Discovery Studio for 3D structure visualization, we performed docking of orientin, a known antidiabetic agent, into the active sites of the target proteins. The resulting binding modes and interactions were extensively analysed to uncover the molecular mechanisms underlying orientin's potential therapeutic effects in diabetes regulation. Our findings demonstrated favourable binding affinities and strong interactions between orientin and the target proteins. Notably, orientin exhibited robust binding to specific nuclear receptors, indicating its potential in activating these receptors and influencing gene expression related to glucose and lipid metabolism. Critical binding sites and residues involved in the drug-target interactions were also identified, providing valuable information for future structure-based drug design and optimization.Overall, our study highlights the potential mechanisms of action of orientin and paves the way for further experimental investigations to validate its therapeutic efficacy in managing diabetes. By utilizing molecular docking analysis, we have gained valuable insights into the interactions between orientin and key proteins involved in diabetes regulation. This contributes to a broader understanding of drug-target interactions and facilitates the development of novel treatments for diabetes.