This study presents the synthesis, spectral analysis and antimicrobial evaluation of a new series of substituted 1,2,4-triazole (5a-i) and 1,3,4-thiadiazole derivatives (9a, c, g, h). New compounds were obtained by cyclization reaction of acyl thiosemicarbazide derivatives in the presence of alkaline and acidic media. All synthesized compounds were screened for their in vitro antimicrobial activities. Nine of the compounds had potential activity against Gram-positive bacteria (MIC = 3.91-500 µg/mL). Some compounds showed good activity especially against: Micrococcus luteus ATCC 10240 (MIC = 3.91-31.25 µg/mL), Bacillus subtilis ATCC 6633 (MIC = 15.63- 62.5 µg/mL), and Staphylococcus aureus ATCC 25923 (MIC = 15.63-125 µg/mL).