Saponins are amphiphilic molecules consisting of carbohydrate and either triterpenoid or steroid aglycone moieties and are noted for their multiple biological activities-Fungicidal, antimicrobial, antiviral, anti-inflammatory, anticancer, antioxidant and immunomodulatory effects have all been observed. Saponins from natural sources have long been used in herbal and traditional medicines; however, the isolation of complexed saponins from nature is difficult and laborious, due to the scarce amount and structure heterogeneity. Chemical synthesis is considered a powerful tool to expand the structural diversity of saponin, leading to the discovery of promising compounds. This review focuses on recent developments in the structure optimization and biological evaluation of synthetic triterpenoid and steroid saponin derivatives. By summarizing the structure-activity relationship (SAR) results, we hope to provide the direction for future development of saponin-based bioactive compounds.