Tripterygium glycosides (TG) are bioactive extracts from the plant Tripterygium wilfordii Hook F. with anti-inflammatory and immunomodulating properties. They have a role in cytokine suppression, autophagy modulation, antifibrotic remodeling and oxidative stress regulation. Clinical and real-world studies support their use in systemic lupus erythematosus, diabetic kidney disease, rheumatoid arthritis, and psoriasis. TGs have a narrow therapeutic window that is overcome by monomer isolation, structural optimization, prodrug strategies and innovative delivery systems. Derivatives such as LLDT-8 (5R-5-hydroxytriptolide) and triptonide have lower toxicity while maintaining efficacy. AI-assisted integration of systems pharmacology, synthetic biology, and drug design is accelerating the development of novel TG therapies.