Chemical investigation of the EtOAc extract of the medicinal plant Thymelaea lythroides yielded eight secondary metabolites, including bassiatin (1), daphenone (2), daphnelone (3), daphnoretin (4), d-sesamin (5), wikstromol (6), trans-tiliroside (7), and rutarensin (8). The structures of the isolated compounds were determined on the basis of 1D and 2D NMR spectroscopy as well as mass spectrometry. Compounds 1–8 were reported from T. lythroides for the first time and the chemotaxonomic significance of these compounds is summarized.