Isoorientin is a natural flavonoid compound found abundantly in various plants, and its potential therapeutic effects have been a subject of scientific interest. In this study, we aimed to investigate the interaction of isoorientin with key enzymes involved in glucose metabolism, namely the insulin receptor (IR), glycogen synthase kinase 3 beta (GSK3β), and glucokinase (GCK), using molecular docking techniques.The molecular docking was performed using AutoDock, employing the crystal structures of IR, GSK3β, and GCK obtained from the Protein Data Bank. Isoorientin was docked into the active sites of these enzymes, and the binding affinities and interaction patterns were analyzed. Our results revealed that isoorientin displayed favorable binding affinities towards all three enzymes. In the case of IR, isoorientin formed hydrogen bonds with key residues involved in ligand recognition, indicating its potential to modulate insulin signaling. Docking into GSK3β showed strong interactions with the ATPbinding pocket, suggesting the compound's potential to inhibit GSK3β activity and subsequent downstream effects on glycogen metabolism and cellular processes. Furthermore, isoorientin exhibited a high binding affinity for GCK, the enzyme responsible for glucose phosphorylation, implying its potential role in regulating glucose uptake and metabolism.The observed interactions suggest that isoorientin may possess antidiabetic properties by modulating insulin signaling, inhibiting GSK3β activity, and promoting glucose metabolism. Further experimental investigations are warranted to validate these findings and unravel the precise molecular mechanisms underlying the effects of isoorientin on glucose homeostasis.