Conventional approaches addressing chronic & acute pains and inflammations are associated with fewer side effects, and there is a need to explore plant-based medicine to mitigate this issue. Sarcostigma kleinii Wight & Arn.is a plant of Western Ghats and not been explored much for its pharmacological and phytochemical profile. Since cellular stress is also involved in the inflammation, various extracts of Sarcostigma kleinii Wight & Arn.seeds were screened for total phenolic, total flavonoid content followed by antioxidant studies by DPPH and Nitric oxide free radical assay. The extracts were also screened for both In vitro and In vivo anti-inflammatory activity. The results suggest that the ethanol extract is moderately safe and exhibited potent inhibition against COX-2 and COX-1 enzymes. The oral administration of the extract was found to significantly reduce the inflammation caused by carrageenan treatment. Compared to the standard Diclofenac the ethanol seed extract effectively reverts the paw edema volume of the inflammatory animals.The phenolic and flavonoid compounds can be interrelated to the antioxidant and anti- inflammatory properties of the plant in the present investigation.