Helicobacter pylori is a Gram-negative human gastric pathogen which has a possible etiologic role in peptic and gastric ulcers, gastric adenocarcinomaand more rarely, lymphoma of the mucosa-associated lymphoid tissue. The pathogenicity of H. pylori is intimately associated with theexpression of virulence factors such as urease, cagA, iceA, vacA and bacterial adhesion and maintenance factors. The cagA, iceA and vacA virulencefactors of H. pylori show great deal of genetic diversity with respect to their ancestor strain, host and environment factors that collectively influence the pattern and severity of the disease. Antimicrobials (triple-therapy regimen) noted to be effective in empirical management of pathogen while emergence of drug resistance remains a major obstacle in eradication of this gastro-duodenal pathogen. In this regard probiotics have great potential of treating H. pylori infection because they exhibit antagonistic activities against many pathogens including H. pylori. Focus of this review is to highlight importance of probiotic micro-organism in improving host defense mechanism. Review also highlights the need of further investigation involving genome wide association studies to unravel the interactions between host, probiotics and bacterial pathogen that would determine fate of pathogen in a complex environment of gastro-duodenal region.