Triptolide, as a key active ingredient in the traditional Chinese medicine Tripterygium wilfordii, has shown significant potential in the treatment of kidney diseases. This article systematically reviews the research progress of its application in the treatment of kidney diseases, covering chemical properties, pharmacological and toxicological mechanisms, and targeted drug delivery strategies. In terms of pharmacological mechanisms, triptolide mainly exerts renal protection through multiple pathways such as protecting podocytes, inhibiting inflammation, and anti fibrosis. However, its significant toxicity is a key limiting factor for clinical applications, involving complex metabolic pathways, signaling pathways, and cellular processes. To enhance therapeutic efficacy and reduce toxicity, researchers have developed various targeted kidney delivery systems, such as delivery systems based on coupling technology, nanoparticles, polymer micelles, liposome modification, and derivative strategies. Although positive progress has been made in current research, in order to ensure safe clinical application, it is still necessary to further elucidate its pharmacological and toxicological mechanisms, and conduct long-term toxicological evaluations of existing strategies for enhancing efficacy and reducing toxicity. These works will contribute to the scientific evaluation of the clinical application prospects of triptolide and lay the foundation for its translational application in the treatment of kidney diseases.