ETHNOPHARMACOLOGICAL RELEVANCE: Semen Strychni (Maqianzi), the seeds of Strychnos nux-vomica L. (family Loganiaceae), is a traditional Chinese herbal medicine known for its anti-inflammatory, analgesic, and anti-tumor properties. However, the clinical application of Semen Strychni has been seriously limited due to its serious central nervous system toxicity and narrow therapeutic window. AIM OF THE STUDY: The research aims to explore the ancient and modern techniques for mitigating toxicity and enhancing efficacy of Semen Strychni, such as processing with auxiliary materials, combined use with herbs, dosage forms and so on. The study seeks to provide a reference for in-depth research and safe clinical use while exploring future development directions and application prospects. MATERIALS AND METHODS: Relevant information from 1957 to 2024 via databases was meticulously collected using the keywords "Semen Strychni", "reduce toxicity and increase efficacy", "preparations" and so on from esteemed scientific databases such as CNKI, PubMed, Google Scholar, and Baidu Scholar, as well as doctoral and master's dissertations and classic texts on Chinese herbs. RESULTS: Many chemical constituents have been identified from Semen Strychni, including alkaloids, terpenoids, organic acids, and others. The toxic effects of Semen Strychni on the nerves, immune, and other systems have also been observed. Existing research has firmly established that brucine and strychnine are the primary sources of its toxicity. To mitigate these risks, the toxicity of Semen Strychni should be reduced prior to use. The most common detoxification strategies include processing and the combined use with other herbs in prescriptions. Furthermore, the development of novel dosage forms offers a new approach to enhance the safety and efficacy of Semen Strychni. However, these methods still possess some limitations, which should be validated and optimized in more diverse experimental and clinical studies. CONCLUSIONS: This review serves to emphasize the urgency of addressing the toxicity concerns of Semen Strychni before considering its clinical application, and systematically summarizes various detoxification strategies employed to date. This study provides valuable insights for enhancing the efficacy and mitigating the toxicity of Semen Strychni. Further research is required to fully elucidate the composition variations and mechanisms existing in these attenuation methods. Such research endeavors contribute to the modernization and standardization of Semen Strychni usage and are of great significance for improving the safety of clinical applications.