The antibiotic resistant crisis is a worldwide phenomenon that threatens the global health. The misuse and overuse of antibiotics as well as the inadequate development of new antibacterial drugs have all drove the evolution of resistance. Thus, the development and discovery of novel antibacterial agents is a critical field within medicinal chemistry. In this study, a series of novel 1,3,4 thiadiazole derivatives containing imine group was synthesized. The chemical structures had been identified by 1H-NMR, FT-IR, Elemental Analysis (CHNS), and some physicochemical properties. The antibacterial activity of the synthesized compounds was evaluated against two gram-positive (Staphylococcus aureus, Enterococcus faecalis), and two gram negative (Escherichia coli, Klebsiella pneumonia) bacteria. Among the synthesized compounds, compounds e4, e5, and e6 were found to exhibit good antibacterial activity against the tested bacterial strains.