The study was aimed at evaluating the antioxidant and free radical scavenging activities ofethanolic extract and its fractions of Cleome rutidosperma. The antioxidant activity, reducingpower, total phenolic content, total flavonoid content, superoxide anion scavenging activity,nitric oxide anion scavenging activity, in vitro antilipid peroxidation activity and in vitro non-enzymatic hemoglobin glycosylation were studied. The results obtained in the study indicate thatCleome rutidosperma is a potential source of natural antioxidant. All the parameters were found tobe concentration dependent and increased with increasing amounts of sample. Flavonoids,phenolic compound like tannins, terpenoids may be responsible for the antioxidant activity of theplant. Variation of solubility parameters in various models may be attributed to non-linearity ofactivity of ethanol extract fractions models. Further investigation on the isolation andidentification of antioxidant component(s) in the plant may lead to chemical entities withpotential for clinical use.