Background: Goniothalamin (GTN) is a well-known styryl lactone that possesses anti-inflammatory and anticancer properties. In this study, we evaluated the potential of GTN on experimental arthritis based on the complete Freund's adjuvant (CFA)-induced arthritis model in rats and the effect was compared with standard drug. Materials and Methods: The animals were divided into six groups: normal, CFA, CFA + indomethacin (10 mg/kg bw), CFA + GTN (50 mg/kg bw), CFA + GTN (100 mg/kg bw), and GTN (100 mg/kg bw) alone. The antiarthritic activity of GTN was measured by paw thickness, arthritic score, body weight, organ weight, biochemical markers, inflammatory mediators, and histopathologic analysis of ankle joints. Results: GTN significantly reduced the paw thickness, arthritic score, body weight changes, and organ weight. It reduced the levels of C-reactive protein, alkaline phosphatase, rheumatoid factor, and proinflammatory cytokines in a dose-dependent manner. It also minimized the histopathologic changes in ankle joints induced by CFA in a dose-dependent manner. Conclusion: These results demonstrate that GTN is effective against inflammation and is an alternative agent for the management of arthritis.