Objective To investigate the similarities and differences in the mechanisms of Huatan drugs and Qushi drugs in treating obesity-related polycystic ovary syndrome (PCOS) and to identify the key active components. Methods Components and targets of Huatan drugs and Qushi drugs were screened by HERB database. The OmicsCloud platform was employed for enrichment analyses of targets by Gene Ontology and Kyoto Encyclopedia of Genes and Genomes. Pathway networks were constructed by Cytoscape 3.8.0 software to visualize pathway differences. PCOS-related key targets were identified by Gene Expression Omnibus database and R 4.2.2 software. Molecular docking techniques were used to predict binding affinities between the key components and targets, followed by validation through molecular dynamics simulations. Results Huatan drugs and Qushi drugs shared 52 active components and 81 targets. Common pathways involved lipid metabolism, insulin regulation, hormonal regulation, and oocyte maturation, aligning with the pathological mechanisms of obesity-related PCOS. Huatan drugs exhibited superior efficacy in hormonal and insulin regulation, while Qushi drugs excelled in vitamin metabolism and anti-inflammatory pathways. Quercetin, β-sitosterol, and stigmasterol were identified as key components. Stigmasterol demonstrated optimal binding with PCOS-associated key targets Churchill domain-containing protein 1 (CHURC1) and tumor necrosis factor ligand superfamily member 11 (TNFSF11), while molecular dynamics simulations confirmed the robust stability of β-sitosterol and TNFSF11 binding. Conclusion This study elucidates potential targets and mechanisms of Huatan drugs and Qushi drugs in treating obesity-related PCOS, providing insights for identifying key active components and guiding clinical application.