Some alkylthio, alkylsulfinyl and alkylsulfonyl-5-(5-nitro-2-thienyl)-1,3,4-thiadiazoles were synthesized and evaluated against Helicobacter pylori. The antibacterial data indicated that most compounds exhibited significant inhibitory activity against H. pylori- more potent than standard drug metronidazole. Among them, 2-ethylsulfinyl-5-(5-nitro-2- thienyl)-1,3,4-thiadiazole was the most potent compound tested against clinical isolates of H. pylori. Generally the SAR of this series of compounds indicated that both the structure of the alkyl pendent and the S, SO or SO2 linker dramatically impact the antibacterial activity against H. pylori.