AbstractDihydropyrimidinones (DHMPs) are the most important pharmacophore in Medicinal Chemistry. The synthetic approach for deriving DHMPs involves the Biginelli reaction or a combination of it with other multi‐component reactions (MCRs). The scaffold has received considerable attention due to its diverse therapeutic activity. This review delves into the exploration of the biological characteristics of DHMPs, which play a pivotal role in various therapeutic areas including “anti‐inflammatory, anti‐HIV, anticancer, antitubercular, antifungal, antibacterial, antihyperglycemic, antihypertensive, anticonvulsant, antimalarial, antioxidant,” reverse transcriptase (RT) inhibitor, antispasmodic, calcium channel blockers, antiproliferative, urease inhibitor, cyclooxygenase (COX‐2), and β‐glucuronidase inhibitor activities. The insights provided in this review have the potential to aid researchers in the formulation of novel drugs, facilitating creation of more resilient, efficient, and safer therapeutic agents with reduced toxicity and minimized adverse effects.