This review summarizes the synthesis, reactivity, and biological applications of coumarins from 2021 to 2023. Coumarins are versatile natural derivatives with significant chemical and pharmacological potential. Recent advances in their synthesis include innovative strategies for functionalization, enabling the incorporation of diverse functional groups and the construction of complex cyclic architectures. These modifications enhance the biological and physicochemical properties of coumarins, making them valuable scaffolds in medicinal chemistry. The unique structure of coumarins allows them to interact with various targets through hydrophobic interactions, π-stacking, hydrogen bonding, and dipole-dipole interactions, leading to promising applications in treating neurodegenerative diseases, cancer, inflammation, and other conditions. The review highlights the synthesis of 3- and 4-substituted coumarins, focusing on methods such as C–H functionalization, photochemical reactions, and metal-catalyzed processes. These approaches have enabled the efficient synthesis of a wide range of coumarin derivatives with diverse functional groups. The reactivity of coumarins is also discussed, emphasizing their ability to participate in various chemical reactions, including cycloadditions, annulations, and cross-couplings, which are crucial for the development of complex molecular structures. In terms of biological applications, coumarins have shown potential in the treatment of neurodegenerative diseases such as Alzheimer's and Parkinson's. They exhibit inhibitory activities against enzymes involved in disease progression, such as acetylcholinesterase (AChE), butyrylcholinesterase (BuChE), glycogen synthase kinase-3 beta (GSK-3β), and Beta-secretase 1 (BACE1). Additionally, coumarins have demonstrated anti-inflammatory and antimicrobial properties, making them promising candidates for further drug development. The review also discusses the use of coumarins in the synthesis of bioactive compounds and their potential as multitarget drugs. Overall, coumarins represent an important class of compounds with broad applications in medicinal chemistry.This review summarizes the synthesis, reactivity, and biological applications of coumarins from 2021 to 2023. Coumarins are versatile natural derivatives with significant chemical and pharmacological potential. Recent advances in their synthesis include innovative strategies for functionalization, enabling the incorporation of diverse functional groups and the construction of complex cyclic architectures. These modifications enhance the biological and physicochemical properties of coumarins, making them valuable scaffolds in medicinal chemistry. The unique structure of coumarins allows them to interact with various targets through hydrophobic interactions, π-stacking, hydrogen bonding, and dipole-dipole interactions, leading to promising applications in treating neurodegenerative diseases, cancer, inflammation, and other conditions. The review highlights the synthesis of 3- and 4-substituted coumarins, focusing on methods such as C–H functionalization, photochemical reactions, and metal-catalyzed processes. These approaches have enabled the efficient synthesis of a wide range of coumarin derivatives with diverse functional groups. The reactivity of coumarins is also discussed, emphasizing their ability to participate in various chemical reactions, including cycloadditions, annulations, and cross-couplings, which are crucial for the development of complex molecular structures. In terms of biological applications, coumarins have shown potential in the treatment of neurodegenerative diseases such as Alzheimer's and Parkinson's. They exhibit inhibitory activities against enzymes involved in disease progression, such as acetylcholinesterase (AChE), butyrylcholinesterase (BuChE), glycogen synthase kinase-3 beta (GSK-3β), and Beta-secretase 1 (BACE1). Additionally, coumarins have demonstrated anti-inflammatory and antimicrobial properties, making them promising candidates for further drug development. The review also discusses the use of coumarins in the synthesis of bioactive compounds and their potential as multitarget drugs. Overall, coumarins represent an important class of compounds with broad applications in medicinal chemistry.