A series of 5-indolylpyrimido[4,5-d]pyrimidinones (4a-h) were obtained by multi-component reaction of 3-formylindole (1), thiobarbituric acid/barbituric acid (2) and thiourea/urea (3) under microwave irradiation in dry media. Secondly, grinding together neat reactants also gave the titled compounds in good yields. All the synthesized compounds have been characterized on the basis of elemental analyses and spectral data (IR, $^1H$ NMR and Mass). Representative compounds were also evaluated for their antimicrobial activity against Rhizopus stolonifer, Fusarium oxysporum, Escherichia coli, and Pseudomonas aeruginosa at different concentrations. Some of the compounds showed promising activity.