Numerous C-21 steroidal glycosides have been isolated from Cynanchum plants. Many of them derive from the aglycone caudatin (CDT) which includes a tetracyclic deacylmetaplexigenin unit and an ikemaoyl ester side chain. CDT can be found in diverse traditional medicines, such as Baishouwu radix used to treat gastro-intestinal disorders. The compound has revealed marked anticancer properties, reviewed here. CDT and its mono-glycoside analogue CDMC display antiproliferative activities against different cancer cell lines in vitro and have revealed significant anticancer effects in tumor xenograft models in vivo. Their mechanism of action is multifactorial, implicating several signaling pathways (Wnt/GSK3/β-catenin, TRAIL/DR5/ER and TNFAIP1/NFκB) which contribute to the antiproliferative, antiangiogenic, antimetastatic and proapoptotic effects of the natural products. CDT also modulates DNA replication, is antioxidant and targets some cancer stem cells. CDT and CDMC are interesting anticancer products, while other CDT glycoside derivatives display antiviral and antifungal activities. Altogether, the present review provides a survey of the pharmacological profiles of CDT and derivatives. The lack of knowledge about the molecular targets of CDT currently limits drug development but the natural product, orally active, warrants further pharmacology and toxicology studies. Copyright © 2021 Elsevier Inc. All rights reserved.