Phytochemical study of the roots of Trigonostemon thyrsoideum led to the isolation of four new oxygenated daphnane-type diterpenoids, trigonosins A-D (1-4), and two new modified daphnanes, trigonosins E and F (5 and 6). The structures and relative configurations were elucidated on the basis of extensive spectroscopic analysis, including 1D and 2D NMR experiments. All compounds isolated were evaluated for their cytotoxicity against HL-60, A549, and MCF-7 human cancer cell lines.