Endometrial cancer (EC) is a common gynecological malignancy for which polycystic ovarian syndrome (PCOS) has been identified as a significant risk factor. Quercetin, a widely distributed natural flavonoid, has demonstrated potential therapeutic effects in managing both PCOS and EC. However, the specific molecular targets of quercetin in the context of PCOS comorbid with EC (PCOS-EC) remain poorly defined. This study aims to elucidate the therapeutic potential of quercetin for treating PCOS-EC using network pharmacology, molecular dynamics simulations, and in vitro assays. The intersection of 379 PCOS-EC-associated targets with 361 quercetin targets identified 47 potential therapeutic targets of quercetin for PCOS-EC. Gene Ontology enrichment analysis revealed the biological functions, while Kyoto Encyclopedia of Genes and Genomes identified the pathways potentially involved in quercetin's effects against PCOS-EC. Protein-protein interaction network analysis highlighted six overlapping targets, namely, ACTB, AKT1, EGFR, ESR1, PTGS2, and TP53. Molecular docking and molecular dynamics simulations indicated that quercetin bound with high affinity to the hub genes, with AKT1 emerging as a central target. In vitro experiments confirmed that quercetin treatment significantly downregulated AKT expression in EC cells. These findings elucidate potential targets and molecular mechanisms through which quercetin exerts its therapeutic effects.