Helicobacter Pylori colonizes the human gastric epithelium and causes diseases such as gastritis, peptic ulcers, and stomach cancer. Undecaprenyl pyrophosphate synthase (UPPs), which catalyzes consecutive condensation reactions of farnesyl pyrophosphate with eight isopentenyl pyrophosphate to form lipid carrier for bacterial peptidoglycan biosynthesis, represents a potential target for developing new antibiotics. In the present study, X-ray structural analysis and computer virtual screening of inhibitors were performed for H. pylori UPPs. The 3-D structure of H. pylori UPPs was solved, with subtle variations from that of E. coli UPPs. Using the structures, two hits identified from 58,635 compounds through computer virtual screening displayed differential activities against H. pylori and E. coli UPPs.