Rheumatoid arthritis (RA), a chronic autoimmune disorder, is characterized by symptoms such as joint swelling and pathological features including synovial inflammation, cartilage degradation, and bone erosion. Recent studies have reported the Nrf2/HO-1 signaling pathway as a crucial regulator of oxidative stress and inflammation in RA. This study focused on the collagen-induced arthritis (CIA) model in DBA/1J mice to investigate whether BAY could ameliorate key symptoms and pathological features of RA by modulating Nrf2/HO-1 signaling. Significant improvements in paw thickness, arthritis scoring, paw withdrawal threshold (PWT), and grip strength (GS) in the BAY-treated CIA group was revealed compared to the CIA group. Additionally, pathological changes were investigated through X-ray imaging, micro-CT analysis, and histological examination of the paw and knee joints. Moreover, BAY treatment upregulated Nrf2/HO-1 signaling, whereas expression of Nrf2 and HO-1 mRNA and protein levels were decreased in the CIA group. Notably, BAY suppressed RA-related inflammatory cytokines while enhancing the antioxidant defense mediated by Nrf2 and HO-1. In summary, this study demonstrated that BAY alleviated bone erosion and inflammation in CIA mice by regulating the Nrf2/HO-1 signaling pathway. Therefore, these findings suggest that BAY could serve as a therapeutic candidate for RA treatment.