In this study, we synthesized and characterized the antibacterial activity of three naturally occurring oxyprenylated chalcones {xinjiachalcone A (1), (2E)-1-{2,6-dihydroxy-4-[(3-methylbut-2-enyl)oxy]phenyl}-3-(4-hydroxyphenyl)prop-2-en-1-one (2), (2E)-1-{2,6-dihydroxy-4-[(3-methylbut-2-enyl)oxy]phenyl}-3-phenylprop-2-en-1-one (3), and lawsone 2-isopentenyl ether (4)}. Using several strains of Helicobacter pylori, including clinical ones, minimum inhibitory concentration (MIC) values and bactericidal activities of these compounds were determined. Xinjiachalcone A (1), active principle of Glycyrrhiza inflata Batalin, was the most effective compound, showing both a low MIC and a strong bactericidal activity against H. pylori. This study suggests that these compounds represent potential natural molecules for the prevention and treatment of H. pylori associated diseases.