The Biginelli reaction is a well-known one-pot multicomponent condensation involving an aldehyde, a β-ketoester, and urea or thiourea for the synthesis of biologically significant 3,4-dihydropyrimidin-2(1H)-ones (DHPMs). In the present study, copper nanoparticles supported on clinoptilolite zeolite (Cu NPs/Clinoptilolite) were employed as an efficient, heterogeneous, and recyclable catalyst for the Biginelli reaction. The catalyst was prepared by depositing Cu nanoparticles onto the porous clinoptilolite framework, providing a high surface area, excellent dispersion of active sites, and enhanced catalytic activity. Various aromatic aldehydes were successfully converted into the corresponding DHPM derivatives under optimized reaction conditions, affording excellent product yields in relatively short reaction times. The catalyst demonstrated remarkable stability and could be recovered and reused for multiple reaction cycles with minimal loss of activity. The enhanced catalytic performance is attributed to the synergistic effect of Cu nanoparticles and the acidic sites of clinoptilolite zeolite, which facilitate carbonyl group activation and promote efficient multicomponent condensation. This environmentally benign protocol offers several advantages, including simple work-up, reduced catalyst loading, high atom economy, excellent selectivity, and easy catalyst recovery, making it a sustainable alternative to conventional homogeneous catalytic systems. The developed methodology provides a green and efficient approach for the synthesis of pharmaceutically important dihydropyrimidinone derivatives.