The study was aimed at evaluating the antioxidant and free radical scavenging activities of ethanolic extract and its fractions of Cleome rutidosperma. The antioxidant activity, reducing power, 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 that Cleome rutidosperma is a potential source of natural antioxidant. All the parameters were found to be concentration dependent and increased with increasing amounts of sample. Flavonoids, phenolic compound like tannins, terpenoids may be responsible for the antioxidant activity of the plant. Variation of solubility parameters in various models may be attributed to non-linearity of activity of ethanol extract fractions models. Further investigation on the isolation and identification of antioxidant component(s) in the plant may lead to chemical entities with potential for clinical use.