In this project we discovered that CAP not only reduces joint swelling in arthritic model mice but also exhibits anti-inflammatory and antiproliferative effects on fibroblast-like synoviocytes (FLS). By synthesizing alkyne-tagged CAP probes and employing activity-based protein profiling (ABPP), we identified and confirmed that CAP binds to PRDX2, inhibiting its antioxidant function and thereby inducing cellular oxidative stress and apoptosis, which contribute to its anti-arthritic effects. Furthermore, we found that the PRDX2 inhibitor, Conoidin A (ConA), produces similar effects. The results indicate that PRDX2 serve as a potential target for capsaicin to therapeutic intervention in rheumatoid arthritis.