Helicobacter species colonizes the stomach and are associated with the development of gastritis disease. Drugs for treatment of Helicobacter infection relieve pain or gastritis symptoms but they are not targeted specifically to Helicobacter pylori. Therefore, there is dire need for discovery of new drug targets and drugs for the treatment of H. pylori. The main objective of this study is to screen the potential drug targets by in silico analysis for the potent strains of H. pylori which include HpB38, HpP12, HpG27, Hpshi470 and HpSJM180. Genome and metabolic pathways of pathogen H. pylori and the host Homosapien sapiens are compared and genes which were unique to H. pylori were filtered and catalogued. These unique genes were subjected to gene property analysis to identify the potentiality of the drug targets. Among the total number of genes analysed in different strains of H. pylori nearly 558, 569, 539, 569, 567 number of genes in HpB38, HpP12, HpG27, Hpshi470 and HpSJM180 found qualified as unique molecules and among them 17 qualified as potential drug targets. Membrane fusion protein of hefABC efflux system, 50 S ribosomal protein L33, Hydrogenase expression protein/formation of HypD, Cag pathogenecity island protein X, Apolipoprotein N acyl transferase, DNA methyalse, Histone like binding protein, Peptidoglycan-associated lipoprotein OprL were found to be critical drug targets to H. pylori. Three (hefABC efflux system, Hydrogenase expression protein/formation of HypD, Cag pathogenecity island protein X) of the 17 predicted drug targets are already experimentally validated either genetically or biochemically lending credence to our unique approach.