Two new cembrane diterpenoids, named populeuphrines A and B (<b>1</b> and <b>2</b>), together with three known analogues (<b>3</b>-<b>5</b>) were isolated from the resins of <i>Populus euphratica</i>. The planar structures and relative configurations of <b>1</b> and <b>2</b> were elucidated by detailed 1 D and 2 D NMR spectroscopic analyses. The absolute configurations of <b>1</b> and <b>2</b> were determined by X-ray diffraction analysis and quantum chemical computation. Biological activities of all the isolates against proliferation of human cancer cells and umbilical cord mesenchymal stem cells were evaluated.