Three undescribed dammarane-type saponins, russelliinosides A-C, together with a common sterol (β-sitosterol), an abietane diterpenoid (18-hydroxyferruginol), two oleane triterpenoids (daturaolone and oleanolic acid), an ursane triterpenoid (ursolic acid) as well as three 5-hydroxyflavones (cirsimaritin, eupatorin, and salvigenin) were isolated from a dichloromethane extract of the aerial parts of Salvia russellii Benth. The chemical structures of the aforementioned compounds were characterized, using detailed spectroscopic analyses, including high-resolution mass spectrometry and 1D and 2D NMR (1H–1H COSY, TOCSY, HSQC, HMBC and NOESY) spectroscopy as well as physicochemical properties. Cytotoxic effects of S. russellii extract and the three isolated russelliinosides were tested against MCF-7 human breast and A549 lung cancer, as well as non-cancer NIH/3T3 cells using MTT reduction assay. Russelliinosides A and B exhibited cytotoxic activities with IC50 values of 7.1 and 30.7 μg/ml against MCF-7 and 33.9 and 69.4 μg/ml against A549 cells, respectively, while russelliinoside C did not show cytotoxicity against cancer cells. On the other hand, russelliinoside A showed an IC50 value of 31.5 μg/ml against NIH/3T3 cells, while russelliinosides B and C had no effect on the viability of these non-cancer cells.