Drimys brasiliensis Miers (Winteraceae), commonly called casca d'anta, is found in the Atlantic Forest and in Cerrado domain. It is considered an important source of natural compounds with pharmacological properties, however little is known about their phytotoxic potential on other plants. This study aims to evaluate the phytotoxic effects of D. brasiliensis leaf extracts collected in two seasons (dry and rainy) on the germination and seedling growth of Sesamum indicum L., as well as evaluating the effect of the most active extract on metaxylem cell size in the roots of the target species. The aqueous extract was prepared with 10 g of dried, ground leaves dissolved in 100 mL of distilled water, resulting in a 10% extract concentrate. Dilutions were made with distilled water to 7.5; 5.0; 2.5% and 0% (control). The leaf extracts showed phytotoxicity on germination and early growth of sesame, with more pronounced activity in leaves collected in the dry season. The inhibitory effects were observed at the cellular level in sesame roots, with a significant reduction in the size of the metaxylem cells in the presence of all concentrations of leaf extract. The extract from leaves of D. brasiliensis may constitute a promising source in the search for natural phytotoxins for use in sustainable agriculture practices.