Two new dihydrochalcones (1, 2), as well as eight known compounds, piperaduncin C (3), 2,6-dihydroxy-4-methoxydihydrochalcone (4), 4,2,6-trihydroxy-4-methoxydihydrochalcone (5), 4-hydroxy-3,5-bis(3-methyl-2- butenyl)-benzoic acid (6), 3,5-bis(3-methyl-2-butenyl)-4-methoxybenzoic acid (7), 4-hydroxy-3-(3-methyl-2-butenoyl)-5-(3-methyl-2-butenyl)-benzoic acid (8), 2,2-dimethyl-8-(3-methyl-2-butenyl)-2H-1-chromene-6-carboxylic acid (9), and 3-(3,7-dimethyl-2,6-octadienyl)-4-methoxybenzoic acid (10) were isolated from the leaves of Piper dennisii Trelease (Piperaceae), using a bioassay-guided fractionation to determine their antileishmanial potential. Among them, compound 10 exhibited the best antileishmanial activity (IC= 20.8 M) against axenic amastigote forms of Leishmania amazonensis, with low cytotoxicity on murine macrophages. In the intracellular macrophage-infected model, compound 10 proved to be more active (IC= 4.2 M). The chemical structures of compounds 1-10 were established based on the analysis of the spectroscopic data. © Georg Thieme Verlag KG Stuttgart · New York.