<p>This research investigated the impact of nevadensin on inflammation, migration, and invasion in TNF-α-induced human rheumatoid arthritis synovial cells (MH7A cells) and adjuvant-induced arthritis in Sprague-Dawley rats. The effects of nevadensin on cell viability, migration, and invasion and the concentrations of pro-inflammatory cytokines and matrix metalloproteinases (MMP-2 and MMP-9) were evaluated in MH7A cells. The results were further investigated in complete Freund’s adjuvant–induced arthritic Sprague-Dawley rats utilizing biochemical and other measures. The findings indicated that nevadensin markedly decreased inflammatory cytokines (IL-1β, IL-6, and IL-8) and MMP-2 and MMP-9 in MH7A cells while preserving cell viability. Nevadensin also impeded the migration and invasion of MH7A cells. In rats, nevadensin administration resulted in a dose-dependent decrease in arthritic score and hind-paw edema relative to complete Freund’s adjuvant animals (**<i>p</i> &lt; 0.01 <i>vs</i>. complete Freund’s adjuvant group). Furthermore, oxidative stress was diminished, evidenced by reduced MDA activity, elevated SOD and GSH levels, and lowered cytokine levels (TNF-α, IL-1β, and IL-6, **<i>p</i> &lt; 0.01 compared to the complete Freund’s adjuvant group). RT-qPCR research has shown that nevadensin significantly reduced TLR4 and NF-κB mRNA levels in complete Freund’s adjuvant–induced arthritic rats (**<i>p</i> &lt; 0.01 compared to complete Freund’s adjuvant group). The data indicate that nevadensin possesses therapeutic potential for rheumatoid arthritis in both <i>in vitro</i> and <i>in vivo</i> models.</p> Graphical Abstract <p></p>