A series of 1-(2-Oxo-2-phenyl-ethyl)-2-phenyl-1H-indole-3yl)methylene) semicarbazone derivatives (4a–g and 6a–c) were synthesized by the condensation of derivatives of 1-(2-Oxo-2-phenyl-ethyl)-2-phenyl-1Hindole-3-carbaldehyde and semicarbazide in ethanol under microwave irradiation procedure. Both conventional and microwave-irradiated syntheses have been carried out to compare their yields and reaction time. The structures of the synthesized compounds were confirmed by spectral data. The antimicrobial activities of the synthesized compounds were screened using broth dilution method. Among all the screened compounds some of the compounds exerted good antifungal activity against C. albicans and C. rugosa. All the compounds exhibited moderate activity against bacteria such as B. subtilis, S. aureus, S. epidermidis, E. coli, P. aeoginosa, and K. pneumoniae.