Nowadays, heterocyclic compounds act as a scaffold and are the backbone of medicinal chemistry. Among all of the heterocyclic scaffolds, 1,4-Dihydropyridine (1,4-DHP) is one of the most important heterocyclic rings that possesses prominent therapeutic effects in a very versatile manner and plays an important role in synthetic, medicinal, and bioorganic chemistry. The main aim of the study is to review and encompass the relevant studies related to 1,4-DHP and excellent therapeutic benefits of its derivatives. An extensive review of Pubmed-Medline, Embase and Lancet’s published articles was done to find all relevant studies on the activity of 1,4-DHP and its derivatives. 1,4-DHP is a potent voltage-gated calcium channel (VGCC) antagonist’s derivatives which acts as the anti-hypertensive, anti-anginal, anti-tumor, anti-inflammatory, anti-tubercular, anti-cancer, anti-hyperplasia, anti-mutagenic, anti-dyslipidemic, and anti-ulcer agent. From the inferences of the study, it can be concluded that the basic nucleus, 1,4-DHP which is a voltage-gated calcium ion channel blocker, acts as a base for its derivatives that possess different important therapeutic effects. There is a need of further research on this basic nucleus as it is a multifunctional moiety, on which addition of different groups can yield a better drug for its other activities such as anti-convulsant, anti-oxidant, anti-mutagenic, anti-microbial activity. This review would be significant for further researches in the development of several kinds of drugs by representing successful matrix for the medicinal agents.