Celastrol, a principal bioactive ingredient of Tripterygium wilfordii Hook F, has gained extensive exploration due to its unique structure features and multiple promising biological activities. This review will focus on the structural modifications, structure-activity relationships, pharmacology, and toxicology of celastrol in the past ten years. We hope this review would be helpful to get a better grasp of the progresses in the field and provide constructive suggestions for the further study of celastrol.