Medicinal and edible Polygonati Rhizoma were used as research materials to analyze the difference of secondary metabolites,and to predict and validate the potential active ingredients and mechanisms for improving insulin resistance (IR) in the differential components.UHPLC-ESI-MS/MS was used to detect the secondary metabolites of medicinal and edible Polygonati Rhizoma.The compounds with the top ten changes in the relative contents of different metabolites and the upregulated metabolites were used for network pharmacological analysis and verified by molecular docking.HepG2 cells were selected for cellular experimental validation using IR model induced by the combination high-glucose medium and high-concentration insulin.319 compounds were identified from the samples,of which 106 were different metabolites.The results of PCA and HCA cluster analysis showed that there were significant differences in the relative content of secondary metabolites between the medicinal and edible Polygonati Rhizoma.Network pharmacological analysis showed that 5 upregulation compounds,such as isorhamnetin,rhoifolin and isorhoifolin,coincided with IR disease targets,and there were 59 intersection targets,mainly involving PI3K-Akt,mTOR,VEGF and other signaling pathways.Molecular docking verification showed that isorhamnetin,rhoifolin and isorhoifolin have good docking with the core targets PI3K,AKT1,VEGFA,mTOR and AMPK,and their binding energy were ≤ -20.9 kJ/mol.Cell experiments showed that isorhamnetin could significantly increase glucose consumption in IR models of HepG2 cells (P<0.01),and increase the protein expression levels of PI3K and AKT1 in IR HepG2 cells,while decrease the protein expression levels of VEGF and mTOR.The results of this study are of great significance for understanding the difference of secondary metabolites between medicinal and edible Polygonati Rhizoma,improving the evaluation method of Polygonati Rhizoma quality and screening of potential active ingredients for improving IR.