In order to find new and potent drug candidates for the treatment of Helicobacter pylori infections‚ in this study attention was focused on the synthesis and anti-H. pylori activity of a series of 5-(5-nitrofuran-2-yl)-1,3,4-thiadiazoles containing piperazinyl functionality at the C-2 position of the 1,3,4--thiadiazole ring. The synthesis of 1-[5-(5-nitrofuran-2-yl)-1,3,4-thiadiazol-2--yl]piperazine derivatives 3a–h and pyrrolidine derivative 3i was achieved with a versatile and efficient synthetic route via 2-chloro-5-(5-nitrofuran-2-yl)-1,3,4--thiadiazole. The inhibitory activity of the new derivatives 3a–i against twenty clinical H. pylori strains was evaluated by the disc diffusion method and compared with the commercially available standard drug metronidazole. Resulting biological data indicated that most compounds exhibited strong inhibitory activity even at doses lower than 2 μg/disc (average zone of inhibition >20 mm) while metronidazole had little or no growth inhibition at this dose. Compound 3c containing the N-benzoylpiperazin-1-yl moiety showed the most potent inhibitory activity.