Saponins are natural glycosides consisting of a triterpene or steroid aglycone with a range of pharmacological properties such as significant anti-tumor activity. In this article, we review our recent progress in the studies of the saponins possessing anticancer effects, especially anti-glioblastoma effects from twelve species of marine organisms and terrestrial plants. The anti-glioblastoma active saponins discovered by other researchers in recent decades are also reviewed and compared. Systematic extraction, isolation and structural elucidation on the saponin constituents from three species of starfishes, five species of sea cucumbers and four species of medicinal plants led to the identification of more than 129 saponins, among which 76 saponins are new compounds. Most of the new compounds were found to possess relatively rare structural features showing in vitro cytotoxicity against tumor cells, especially glioblastoma cells. Several saponins exhibited significant anti-glioblastoma effects in vivo by in situ administration (interstitial chemotherapy) and their haemolytic side effects were avoided in the tests. Multiple mechanisms of action, such as interfering with cell cycle progression, inducing apoptosis, promoting stabilization of microtubule, as well as several signal transduction pathways, were involved in their anticancer effects. The review provided valuable leads for pursuing new anti-glioblastoma drugs, and established a new viewpoint for further development of these marine and terrestrial organisms. The successful approach to administrate saponins in situ conquered the bottleneck in the development of saponins as new drugs- haemolytic effects. It means that saponins may be developed as potential chemotherapeutic agents in pursuing new antiglioblastoma drugs.