This study reports a highly efficient, sustainable, and step-economical approach for the synthesis of biologicallyrelevant dihydropyrimidinones (DHPMs) via a multicomponent Biginelli reaction catalysed by sulfonatednaphthalene formaldehyde (SNF) in an aqueous medium. Under optimised conditions (10 wt%SNF in water at 80 °C), an array of eleven structurally diverse DHPM derivatives was obtained in good to excellent yields (73–95%) within short reaction times. Beyond optimising operational metrics, this research directly addresses a persistent challenge in modern synthetic chemistry: reducing the discipline's heavy reliance on toxic, metal-based catalysts andhazardous volatile organic solvents. Eleven diverse DHPM derivatives were obtained in good to excellent yields. The water-soluble catalyst could be reused with slight activity loss, and the process highlights green chemistrybenefits through aqueous medium, operational simplicity, and partial catalyst recyclability. Aligning seamlesslywithglobal sustainability mandates, this work is closest to ‘Responsible Consumption and Production,’ SDG, offeringaconcrete advancement toward safer, eco-compatible chemical production practices