In the present work, some new 1,3,5-trisubstituted[1,2,4]triazole derivatives and their Schiff's bases were synthesized. The chemical structure of the target compounds was confirmed by IR, 1H-NMR, 13C-NMR, FAB-MS, EI-HRMS spectra and elemental analyses. The title compounds were tested for their in vitro antibacterial activity against Gram-positive and Gram-negative ones using ampicillin and nalidixic acid as reference drugs. Some of them showed antibacterial activity more significant than the reference drugs.