Herbicide safeners, highly effective antidotes, find widespread application in fields for alleviating the phytotoxicity of herbicides to crops. Designing new herbicide safeners remains a notable issue in pesticide research. This review focuses on discussing and summarizing the structure-activity relationships, molecular structures, physicochemical properties, and molecular docking of herbicide safeners in order to explore how different structures affect the safener activities of target compounds. It also provides insights into the application prospects of computer-aided drug design for designing and synthesizing new safeners in the future.