Objective To explore the mechanism by which osteoking (OK) regulates ferroptosis and improves osteoarthritis. Method: Perform KEGG pathway enrichment analysis by analyzing target genes related to OK, OA, and ferroptosis through network pharmacology. In vivo experiments were conducted using medial meniscus instability surgery to construct a rat model of knee osteoarthritis (KOA). A sham surgery group (sham group), a model group (DMM), and osteoking group (OK) were set up, and corresponding drugs were administered orally for 8 weeks according to the grouping. Record the paw contraction reaction time (s) and weight (g) of each group of rats using a hot plate apparatus and a pressure pain gauge, respectively. ELISA kit was used to detect serum inflammatory factors TNF-α, VEGF, IL-6 and oxidative stress factors MDA, SOD, GSH, ROS in rats. Stain the knee joints of rats with eosin hematoxylin, safranin turquoise, and toluidine blue, and score the degree of cartilage tissue degeneration according to the OARSI standard. Western blot was used to detect the expression of extracellular matrix degradation protein 13(MMP13), cartilage matrix synthesis protein 2 (COLA2), glutathione peroxidase 4 (GPX4), solute carrier family 7 member 11 (SLC), advanced glycation end products (AGE), and their receptor (RAGE) proteins in rat cartilage. Using 10 mg/L IL-1β to induce human C28/I2 cells to simulate an in vitro model of arthritis, the cells were divided into control group, model group (IL-1β), OK group, and OK+AGEs group.ELISA kit was used to detect the inflammatory factor IL-6 and oxidative stress factors MDA, SOD, and GSH in the cell supernatant. Cell specific Fe2+assay kit was used to detect the content of each group of cells. Western blot was used to detect MMP13, COLA2, GPX4, and SLC11 proteins. Results The network pharmacology analysis revealed that AGE-RAGE signaling pathway and other pathways may be key pathways for OK to act on osteoarthritis and ferroptosis. In animal experiments, the model group rats showed significant increases in tenderness (P<0.01), thermal pain value (P<0.01), and OARSI score (P<0.001), as well as damage to the cartilage surface and cartilage matrix of the knee joint. Compared with the model group, OK significantly reduced tenderness, thermal pain, and OARSI scores in rats (P<0.01), alleviating damage to the cartilage surface and cartilage matrix of the knee joint. Compared with the model group, the expression of COLA2, GPX4, and SLC11 proteins in the articular cartilage of the OK group significantly increased (P<0.1), while the expression of MMP13 (P<0.1), AGEs (P<0.01), and receptor RAGE (P<0.01) decreased. The serum levels of TNF-α, VEGF, IL-6, MDA, and ROS in the OK group were significantly reduced (P<0.01), while SOD and GSH increased (P<0.01). In cell experiments, the levels of MDA (P<0.05), IL-6, and Fe2+increased in the IL-1 β group (P<0.01), while the levels of GSH (P<0.05) and SOD decreased (P<0.01); The protein levels of MMP13 increased (P<0.05), while the protein levels of COLA2, GPX4, and SLC11 decreased (P<0.01). OK intervention reverses the above results, improves oxidative stress and chondrocyte metabolic balance, reduces inflammatory factors, iron load, and ferroptosis. AGEs weakened the effect of OK, and the relevant indicators had statistical significance. In addition, OK further enhances the anti-inflammatory and antioxidant stress effects of ferroptosis inhibitor Fer-1 on C28/I2 cells, and improves metabolic balance. Conclusion OK can inhibit ferroptosis and protect articular cartilage through the AGEs-RAGE axis, thereby exerting anti arthritis effects.