Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by persistent joint inflammation and progressive cartilage and bone destruction. Oxidative stress and inflammatory signaling contribute to RA pathogenesis, with the Nrf2/NF-κB axis regulating redox homeostasis and inflammation. This study investigated the protective effects of acteoside (ACT) against RA-associated pathology and its involvement in Nrf2/NF-κB signaling. In a collagen-induced arthritis (CIA) mouse model, ACT reduced paw swelling, arthritis scores, and pro-inflammatory cytokine expression and improved pain-related behaviors. Micro-CT and histological analyses demonstrated reduced bone erosion and cartilage damage. In bone marrow-derived macrophages, ACT suppressed RANKL-induced osteoclastogenesis and bone resorption, whereas these effects were reversed by H₂O₂ and the Nrf2 inhibitor ML385. In SW1353 chondrocyte-like cells, ACT reduced H₂O₂-induced reactive oxygen species production and cell death and attenuated IL-1β-induced matrix metalloproteinase activity. Collectively, ACT alleviated joint inflammation and structural damage, suppressed osteoclastogenesis, and protected chondrocyte-like cells from oxidative and inflammatory injury. These effects were associated with modulation of Nrf2/NF-κB signaling, supporting the therapeutic potential of ACT for RA.