A series of Schiff’s bases i.e., N-(p-substituted benzylidene)-5-methyl-1, 3, 4-thiadiazole-2-amines were synthesized from 2-amino-5-methyl-1, 3, 4-thiadiazole 1 and studied for their in vitro antibacterial activity. Reaction of thiosemicarbazide with glacial acetic acid in presence of concentrated sulphuric acid led to the formation 1 which on further reaction with different p-substituted benzaldehydes yielded the title compounds 2. These compounds were characterized by spectral analysis. All the synthesized compounds were evaluated for their in vitro for their antibacterial activity against two Gram positive bacterial strains (Bacillus subtilis and Staphylococcus aureus) and two Gram negative bacterial strains (Escherichia coli and Pseudomonas aeruginosa) and their minimum inhibitory concentration (MIC) were determined.