A new series of indole-based chromene derivatives 4a–4p has been synthesized by one pot cyclocondensation reaction of 2-phenyl-1H-indole-3-carbaldehyde 1a–1h; malononitrile 2; and 1,3-cyclohexanedione/dimedone 3a/b under microwave irradiation catalyzed by an organocatalyst 4-(N,N-dimethylamino) pyridine. Easy experimental procedure, high yield, selectivity, and shorter reaction time are the imperative features of this method. All the compounds were screened against a representative panel of bacteria and fungi. Some of the compounds are found to be equipotent or more potent than that of standard drugs as evident from SAR study.