Abstract Synthesis of a new series of bis-heterocyclic chalcone derivatives has been reported. The condensation proceeded by the one-pot reaction of N-phenyl succinimides and 4-hydroxy-3-methoxy benzaldehyde in the presence of neutral alumina under microwave irradiation. The advantages of this method are high yield, shorter reaction time, and simple workup procedure. Most of the synthesized compounds have shown moderate to significant antimicrobial activity against different microbial strains.