The Indian system of medicine provides Strychnos potatorum Linn. seeds for the treatment of various ailments like jaundice, bronchitis, diabetes, renal and vesicle calculi, conjunctivitis, chronic diarrhoea, dysentery etc. The present study involves the effect of crude powder (SPP) and aqueous extract (SPE) of S. potatorum Linn seeds on in vivo antioxidant defense system against Freund’s complete adjuvant (FCA) induced arthritis in rats at the dose of 200 mg/kg/p.o for 14 and 28 days and in vitro antioxidant activity against Ferrous thiocyanate (FTC) and Thiobarbiturate (TBA) induced lipid peroxidation. The antioxidant defense system parameters studied in plasma and tissues of arthritic rats were found to be altered significantly. These alterations observed in arthritic rats may be due to the increased oxidative stress in the tissues, which were significantly reduced in SPP and SPE treated arthritic rats. The results reveal that, the drug treatment decreased the LPO levels in plasma and tissues, either by interception of the formation or by scavenging the active oxygen species. The raise in enzymic and nonenzymic antioxidants level may be due to the sparing effect of antioxidant defense system as the drugs SPP and SPE have scavenged the free radicals by various antioxidant phytochemicals like steroids, triterpenes and polyphenolics present in it either by individual or by combined action. In in vitro total antioxidant analysis by FTC and TBA methods, SPE was found to show higher antioxidant activity when compared with SPP. Key words: Strychnos potatorum, enzymic and non-enzymic antioxidants, free radical scavenging, lipid peroxidation.