Radix Bupleuri (RB) has been widely used in Chinese Traditional Medicine for over 2000 years and is currently marketed in China as Chai-Hu-Shu-Gan tablets and Xiao-Yao-Wan tablets. Saikosaponins (SSs, especially SSa, SSc and SSd), as the major bioactive compounds in RB, represent anti-inflammatory, anti-tumor, anti-oxidant, anti-viral and hepatoprotective effects. To summarize recent findings regarding to the extraction, detection, biosynthesis, metabolism, pharmacological/toxicological effects of SSs. Online academic databases (including PubMed, Google Scholar, Web of Science and CNKI) were searched using search terms of “Saikosaponin”, “Radix Bupleuri”, “Bupleurum” and combinations to include published studies of SSs primarily from 2003 to 2018. Several critical previous studies beyond this period were also included. 354 papers were found and 165 papers were reviewed. SSs have drawn great attention for their anti-inflammation, anti-viral and anti-cancer effects and contradictory roles in the regulation of cell apoptosis, oxidative stress and liver fibrosis. Meanwhile, increased risks of overdose-induced acute or accumulation-related chronic hepatotoxicity of SSs and RB have also been reported. However, underlying mechanisms of SSs bioactivities, the metabolism of SSs and bioactivities of SSs metabolites are largely unknown. This comprehensive review of SSs provides novel insights and perspectives on the limitations of current studies and the importance of metabolism study and the dose-pharmacological/toxic relationship of SSs for the future discovery of SSs-based therapeutic strategies and clinical safe practice. Display omitted