RNA molecules are crucial in many biological processes, therefore, they have become potential targets for disease diagnosis and treatment. The design of small molecules that can target RNA structures is a promising approach, as they are tunable and easily taken up by cells. However, it can be challenging without knowing the RNA structure. In this short opinion letter three different examples will be discussed of research groups combining AI to predict the interactions between RNA molecules and small molecules to address the challenges in designing RNA-targeted ligands due to the difficulty in obtaining accurate RNA structures and the lack of understanding of binding kinetics.