Protulaca oleracea, a widely distributed weed, has been reported to exhibit different health promoting effects. The objective of this study was to evaluate the anti-oxidative and anti-inflammatory effects of P. oleracea on LPS-stimulated AGS cells. The cytotoxicity of P. oleracea in AGS cells was examined by MTT assay. The anti-oxidative effects of P. oleracea were examined by DPPH assay. RT-PCR was carried out to examine the effect of P. oleracea in the mRNA expression of different inflammatory mediators. MTT assay revealed that P. oleracea have almost no cytotoxity in AGS cells. DPPH radical scavenging activities were better than butylated hydroxyl toluene (BHT). The mRNA expression of different endogenous anti-oxidative enzymes (SOD2, GPx3 and catalase) were preserved by P. oleracea in AGS cells. The nitric oxide production and expression of iNOS in LPS stimulated RAW264.7 were suppressed in P. oleracea treated groups. Based on these findings, P. oleracea has protective anti-oxidant and anti-inflammatory effects.