Helicobacter pylori has been known to provoke gastric inflammation, ulceration, and DNA damage, based on which WHO defined H. pylori as a class I carcinogen. Although ginseng, the root of Panax ginseng C.A. Meyer, has been reported to possess antiadhesion or antimicrobial activity against H. pylori, in this study, we examined the protective effect of red ginseng extracts (RGE) against H. pylori-induced cytotoxicity and DNA damage. RGE significantly attenuated both H. pylori-induced DNA damage assessed by comet assay and apoptosis measured by DNA fragmentation. Inactivation of ERK1/2 signaling and attenuation of caspase-3 activation and PARP cleavage were revealed with RGE against H. pylori infection. RGE decreased H. pylori-stimulated IL-8 gene expression, which resulted from the transcriptional regression of NF-kappaB. In conclusion, RGE showed significant gastroprotective effects against H. pylori-associated gastric mucosal cell damage, suggesting that red ginseng could be used as a medicinal phytonutrient against H. pylori infection.