Due to their extensive applications in pharmaceuticals and natural substances, organic synthesis and heterocyclic compounds have been at the forefront of research for many years. Pyrimidine is one of the heterocyclic compounds that have various derivatives with promising biological and pharmacological properties. This review article covers the synthesis and biological effects of pyrimidine derivatives, such as pyrano[2,3‐d]pyrimidines, pyrido[2,3‐d]pyrimidines, and furo[2,3‐d]pyrimidines. The compounds discussed in this review have a wide range of biological activities. Recent advances in green chemistry have led to the development of eco‐friendly synthetic methods for producing these bioactive heterocycles. This review aims to present various synthetic methods and biological effects of these compounds and provide new opportunities for organic chemists to develop potent nitrogen‐ and oxygen‐containing heterocycles for future applications. The review highlights examples of successful syntheses and applications of pyrimidine derivatives in the fields of antibacterial, antifungal, anticancer, enzyme inhibition, and antiviral research.