A new oxygenated spiroketone, isodonspiroketone (1), and 4 known ones (2-5) were isolated from the whole plant of Isodon ternifolius (D.Don) Kudô. The structure of isodonspiroketone (1) was determined by nuclear magnetic resonance, mass spectroscopy, and circular dichroism spectral data. Compound 3 has not been previously isolated from I. ternifolius. Their cytotoxic activities were evaluated against A549, HepG2, and MDA-MB-231 cancer cell lines in vitro. New compound (isodonspiroketone, 1) showed moderate cytotoxic activities against A549, HepG2, and MDA-MB-231 cancer cell lines with half-maximal inhibitory concentration values of 23.84 ± 2.73, 27.77 ± 3.01, and 17.26 ± 1.61 μM, respectively; meanwhile, the others were inactive.