Starting from (5-nitrofuran-2-yl)methylene diacetate, a new series of 2-[(substituted benzyl)thio]-5-(5-nitro-2-furyl)-1,3,4-thiadiazoles (6a-n) were synthesized and the structures of the compounds were determined using spectroscopic methods including mass spectrometry, (1)H-nuclear magnetic resonance, infrared spectroscopy, and elemental analysis. The in vitro anti-Helicobacter pylori activity of the synthesized compounds was evaluated by the disk diffusion method against the clinical isolates of Helicobacter pylori. The results indicated that most of the synthesized compounds exhibited significant inhibitory activity against H. pylori with respect to standard drug metronidazole. Compound 6l, containing the 2-chloro-6-fluorobenzylthio moiety, was the most potent compound tested.