Triptolide is a bioactive diterpenoid lactone from traditional Chinese medicine with notable anti-tumor, immunosuppressive, and anti-inflammatory properties. However, its clinical utility is hampered by poor solubility, a narrow therapeutic index, and multi-organ toxicity. In response, extensive efforts have been made to improve its efficacy and safety profile. This review critically examines recent progress in Triptolide research, covering its mechanisms of action, derivative design, drug delivery systems, and cancer-specific applications. It also evaluates its clinical potential against pancreatic, breast, and ovarian cancers, addresses ongoing challenges, and suggests future research paths to accelerate clinical translation. This article presents a narrative review summarizing the research progress on the pharmacological activities, structural modifications, and nanodelivery systems of Triptolide. Literature searches were conducted in PubMed and Web of Science using keywords including "Triptolide", "pharmacological activity", "structural modification", and "nanodelivery", combined with Boolean operators. The search timeframe was from database inception to March 2026. Inclusion criteria were: original research articles related to the pharmacological activities, structural modifications or nanodelivery systems of Triptolide, peer-reviewed journal articles published in English or Chinese. Exclusion criteria were: duplicate publications, conference abstracts, dissertations, and preprints, articles irrelevant to the topic. Study selection was performed independently by two reviewers, with disagreements resolved through discussion or consultation with a third reviewer. A total of 158 articles were included in this review.