In the past decades, a great number of stimuli-responsive systems have been developed to be used as drug-delivery systems with high sensitivity and selectivity in targeted therapy. Despite promising results, the current stimuli-responsive systems suffer from the complexity of preparation, as most novel stimuli-responsive systems are based on polymers. Small molecules have often been neglected as candidates for application for stimuli-responsive systems. Recently, structures based on six-membered ring molecules or bicyclic molecules have been developed into conformational switches working through conformational interconversion. These single conformational switches have significantly reduced the complexity of material preparation compared to polymers or copolymers. In this review, we focus on ring-system-based conformational switches that are involved in sensors and smart drug-delivery systems. We hope that this review will shed light on ring-system-based single conformational switches for use in the development of stimuli-responsive systems.