An emerging consensus underscores the importance of oxidative events in vascular disease including excess production of reactive oxygen/nitrogen species (ROS/RNS), in addition to lipoprotein oxidation. Sesamum indicum has long been used extensively as a traditional food. The aim of present study was to evaluate antioxidant action of aqueous and ethanolic seed extracts from S. indicum using various in vitro ROS/RNS generated chemical and biological models. Results demonstrated that the graded-dose (25-1000 microg/ml) of aqueous and ethanolic extracts markedly scavenged the nitric oxide, superoxide, hydroxyl, 1,1-diphenyl-2-picrylhydrazyl and 2,2'-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid) radicals and, showed metal chelating ability as well as reducing capacity in Fe(3+)/ferricyanide complex and ferric reducing antioxidant power assays. In biological models, both extracts were found to inhibit metal-induced lipid peroxidation in mitochondrial fractions, human serum and LDL oxidation models. In lipoprotein kinetics study, both extracts significantly (P<0.05) increased lag phase time along with reduced oxidation rate and conjugated dienes production. Ethanolic extract of S. indicum showed higher amounts of total polyphenol and flavonoid content as compared to their counterpart. The IC(50) values of both extracts were compared with respective antioxidant standards. Overall, ethanolic extract of S. indicum possess strong antioxidant capacity and offering effective protection against LDL oxidation susceptibility.