Abstract: Conformational restriction has become one of the important strategies for modification and optimization of lead compounds in structure-based drug design. In this review, we select some recent practical examples from literature to present applications of conformational restriction in structure-based drug design. By introducing fused rings, macrocycles, spiral rings, cyclopropyl groups, bridging rings, methyl groups into molecules, we can find that the conformational restriction strategy is widely used in improving pharmacokinetic properties, enhancing the activity and selectivity, and increasing the novelty of compounds. By using these conformational restriction strategies, the drug-like properties of lead compounds can be significantly improved. This paper can help to provide theoretical guidance and practical experience for innovation in drug design and development.