Dihydropyrimidinone nucleus is an important pharmacophore in medicinal chemistry. The synthesis of dihydropyrimidinone derivatives remains a main focus of modern drug discovery. In the present study, a series of novel dihydropyrimidinone derivatives have been synthesized via Biginelli reaction. The compounds were characterized by FT-IR, 1H NMR analysis, 13C NMR and MASS analysis. The compounds have been evaluated in-vitro for their antimicrobial activity against various strains of gram positive bacterial and fungal strains. The studies revealed that the newly synthesized derivatives exhibited moderate to good antibacterial and antifungal activity.