A new series of N-methyl-5-substituted-1H-indole-2-oxo-3-((2¢ -acetamidothiazol-4¢ -yl)carbonylmethyl hydrazones) (5a-j) were synthesized with high degree of purity and in excellent yield. The structures of new compounds were determined by analytical and spectral methods (IR, 1H NMR, 13C NMR, EIMS). Newly synthesized compounds were tested for their antimicrobial activity were also carried out against three Gram-positive bacteria (Staphylococcus aureus, Bacillus subtilis and Staphylococcus epidermis) and four Gram-negative bacteria (Escherichia coli, Pseudomonas aeruginosa, Salmonella typhi and Klebsiella pneumoniae) and against four fungi (Aspergillus niger, Aspergillus fumigatus, Aspergillus flavus and Candida albicans). Bioassay results showed that most of the synthesized compounds exhibited significant activity against Aspergillus fumigatus, Aspergillus flavus and Candida albicans. Interestingly, among all the compounds, 5c, 5g-h and 5i have shown activity greater than the standard drug miconazole against the fungal strain Aspergillus fumigatus in vitro.