Three saponin glycosides have been isolated and characterized from Teucrium polium L. (Lamiaceae). The compounds were isolated from a MeOH aerial plant extract. The structures were elucidated based on spectroscopic methods including UV, IR, 1D and 2D NMR, and HRESIMS data analyses. The identified compounds were evaluated for anticancer effects against 60 human tumor cell lines (NCI). The triterpene glycoside, poliusaposide C completely inhibited the growth of a breast and colon cancer cell line and partially inhibited the growth of a colon, renal and melanoma cell line. Structure–anticancer activity relationships are discussed.