<p>Researchers are investigating environmentally friendly and sustainable synthetic methods for the development of biologically active organic molecules. In this context, ionic liquids are consistently the preferred option due to their dual function as both catalyst and solvent in organic reactions. They have been extensively employed in the literature for the synthesis of several organic frameworks. Pyrimidine is a distinguished structure among organic compounds that integrates with the structural components of deoxyribonucleic acid and ribonucleic acid. Pyrimidine and its analogs have also significant use in medical, materials, and various scientific sectors. Given its significance, there is an intention to produce an increasing number of pyrimidine derivatives that address societal issues. In recent decades, ionic liquids have been afforded a variety of pyrimidine scaffolds by the implementation of safer and environmentally acceptable methods. This review is the first report detailing the function of ionic liquids as catalysts and solvents in the synthesis of pyrimidine-based molecular hybrids.</p> Graphical abstract <p></p>