It is imperative to interrupt the link between arthritis and regulation of oxidative stress with the administration of antioxidants. Suramin is known for its anti-inflammatory, antineoplastic and antiangiogenic activities implying its possible antioxidant property. In this study, the antioxidant activity of suramin in cell free system was found to be higher than l-ascorbic acid (l-AA) with respect to its scavenging effect on nitric oxide (NO), hypochlorous acid and hydrogen peroxide radicals. Besides, suramin was found to be nontoxic to cultured RAW cells even at high concentrations along with marked inhibition of NO production. Suramin was found to curb the inflammation associated with the collagen induced arthritis (CIA) model. Administration of suramin significantly reduced the malondialdehyde and protein carbonyl content in joints, liver, kidney and spleen of rats as studied ex vivo. Furthermore, the increased antioxidant enzymes such as SOD, catalase, GST, GPx and GR activities in the tissues were restored significantly after suramin treatment. In silico experiments using Vlife MDS4.4-GRIP docking method showed strong affinity of suramin towards erythrocyte catalase followed by glutathione peroxidase thus corroborating with the findings of antioxidant enzyme assays. Our studies clearly indicate that suramin has remarkable antioxidant potential and can ameliorate arthritis via modulation of oxidative stress.