In this study, the antioxidant and anti-inflammatory activities of Salicornia herbacea were evaluated. The crude $CH_2Cl_2$/methanol extract of S. herbacea showed 52% and 86% scavenging activities of the authentic $ONOO^-$ and $ONOO^-$ from 3-morpholinosydnomimine (SIN-1) at a concentration of $50;{mu}g/mL$, respectively, and was subjected to a further fractionation with n-hexane, 85% aqueous methanol, n-butanol, and water. Additional purification of the n-butanol fraction revealed that the most potent scavenging activity led to the isolation of isorhamnetin 3-O-$eta$-D-glucopyranoside as the active principle. The structure of isorhamnetin 3-O-$eta$-D-glucopyranoside was elucidated by extensive two-dimensional nuclear magnetic resonance experiments such as $^1H$ correlation spectroscopy nuclear Overhauser effect spectroscopy, heteronuclear single quantum correlation, and heteronuclear multiple-bond correlation as well as by comparison with the published spectral data. Isorhamnetin 3-O-$eta$-D-glucopyranoside exhibited dose-dependent scavenging activities of the authentic $ONOO^-$ and $ONOO^-$ from SIN-1. The electron spin resonance spin-trap techniques confirmed that reactive oxygen species, including the hydroxyl, superoxide, carbon-centered, and 1,1-diphenyl-2-picrylhydrazyl radicals, were actively quenched by addition of isorhamnetin 3-O-$eta$-D-glucopyranoside. In addition, isorhamnetin 3-O-$eta$-D-glucopyranoside suppressed the lipopolysaccharide-induced nitric oxide production and the expression of cytokines such as inducible nitric oxide synthase, tumor necrosis factor-a, and interleukin-$1{eta}$ in Raw 264.7 cells. Findings from this study should underscore the nutraceutical value of S. herbacea-derived isorhamnetin 3-O-$eta$-D-glucopyranoside as a potent antioxidative and anti-inflammatory agent via alleviation of radical-induced toxicities and pro-inflammatory responses.