The study investigated the traditional Chinese formula BGJXF in the treatment of knee osteoarthritis using a combination of chemical analysis, network pharmacology, molecular docking, and both in vitro and in vivo experiments. LC–MS analysis revealed that BGJXF contains 91 chemical components, of which network pharmacology identified 62 common therapeutic targets for BGJXF and knee osteoarthritis, significantly involved in AGE-RAGE and HIF-1 signaling pathways. Molecular docking identified dehydrocorydalin as a key component with high binding affinity to IL-6, BCL2, MMP9 and CCND1 proteins. In cellular (in vitro) experiments, dehydrocorydalin suppressed LPS-induced overexpression of NF-κB p65 and TNF-α in human chondrocytes. In a rat model of papain-induced knee osteoarthritis, administration of BGJXF significantly reduced serum levels of IL-1β and IL-6, attenuated cartilage structural damage and inflammatory cell infiltration by histopathology. Immunofluorescence showed that BGJXF affects the inflammatory tissue microenvironment and tissue heterogeneity in the joint. The authors conclude that the anti-osteoarthritic effects of BGJXF, mediated mainly by dehydrocorydalin, are related to the multi-target inhibition of the NF-κB inflammatory pathway and to the modulation of "glycometabolic stress-hypoxic damage" via the AGE-RAGE and HIF-1 pathways.