Abstract： Objective： To explore the potential therapeutic targets and mechanisms of Zhuanggu Tongbi Pills in treating knee osteoarthritis （KOA） based on network pharmacology and molecular docking verification. Methods：The active components of Zhuanggu Tongbi Pills were screened using databases such as Taiwan Traditional Chinese Medicine Database （TCM Database@Taiwan）， Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform（ TCMSP），Encyclopedia of Traditional Chinese Medicine（ ETCM），Traditional Chinese Medicine Identification and Network Pharmacology System （TCM Suit），and A high-throughput experiment- and reference-guided database of traditional Chinese medicine （HERB）. The targets of these active components were identified using TCMSP and Swiss Target Prediction databases. Disease-related targets were obtained from DrugBank， Pharmacogenomics Knowledge Base （PharmGKB）， Online Mendelian Inheritance in Man （OMIM）， DisGeNET， GeneCards， Comparative Toxicogenomics Database （CTD）， and Therapeutic Target Database （TTD）. A "drug-active component-target" regulatory network was constructed using Cytoscape software， followed by protein-protein interaction （PPI） network construction and topological analysis. Gene Ontology （GO） and Kyoto Encyclopedia of Genes and Genomes （KEGG） enrichment analyses were performed using the INPUT platform. Molecular docking was conducted using AutoDock Vina for validation. Results：A total of 269 active components，including quercetin，luteolin，kaempferol，and gomisin B， were identified in Zhuanggu Tongbi Pills， corresponding to 1 319 target genes. There were 8 816 KOA-related targets， with 969 overlapping targets. The PPI core network included 138 proteins such as PTGS2， AR， ESR1， NOS2，NCOA2，and CDK2. GO enrichment analysis revealed 3 303 significantly enriched biological processes （BP）， 116 cellular components （CC）， and 244 molecular functions （MF） （P. adjust＜0.05）. KEGG pathway analysis identified 177 significantly enriched pathways （P. adjust＜0.05）， including lipid and atherosclerosis pathways， phosphoinositide 3-kinase-protein kinase B （PI3K-Akt） pathways， mitogen-activated protein kinase （MAPK） pathways， and advanced glycation end products-receptor for advanced glycation end products （AGEs-RAGE） signaling pathways. Molecular docking results showed that quercetin and kaempferol had strong binding affinities with key targets such as PTGS2，AR，and ESR1. Conclusion：Zhuanggu Tongbi Pills in the treatment of KOA primarily through multiple components such as quercetin and kaempferol，acting on targets like PTGS2，AR，and ESR1 across various signaling pathways，including lipid and atherosclerosis and PI3K-Akt pathways.