Background:: This review elaborates the updated synthetic and pharmacological approaches of a known group of dihydropyrimidinones/thiones from the multi-component reaction like Biginelli reaction was named Pietro Biginelli in 1891. This review consists of the reaction of an aromatic aldehyde, urea and ethyl acetoacetate leading to dihydropyrimidinone/thione. Currently, the scientific movement to develop economically viable green methods using compounds that are reusable, non-volatile, easily obtained, etc. Objective:: This review covers the recent synthesis and pharmacological advancement of dihydropyrimidinones/thiones moiety, along with covering the structure-activity relationship of the most potent compounds, which may prove to become better, more efficacious and safer agents. Thus, this review may help the researchers in drug designing and development of new Dihydropyrimidinones entities. Conclusion:: This review focuses on the wide application of dihydropyrimidinone/thione review reports the design, synthesis and pharmacological activities of nitrogen-sulphur containing dihydropyrimidinone moiety by using multi-component reaction. Dihydropyrimidinones (DHPM) pharmacophore is an important heterocyclic ring in medicinal chemistry. It is derived from multi-component reactions, “Biginelli reaction” and plays critical role as anticancer, antioxidant, antimicrobial, antiinflammatory, anti-HIV-1, antimalarial, anti-inflammatory, antihypertensive and anti-tubercular agents. Exhaustive research has led to the determination of its vast biological profile, with a wide range of therapeutic application.