Calophyllum rivulare is an endemic tree from Cuba that belongs to Clusiaceae family.This plant had revealed it to be a rich source of pyranochromanone acids including compounds with a variety of biological potentialities such as antioxidant, antiulcer, anticancer and anti-Helicobacter pylori activities.Herein, antileishmanial and cytotoxic activities of extracts obtained from C. rivulare leaves (rich in pyranochromanone acids) and amentoflavone were compared.Extracts were prepared by maceration employing ethyl acetate (CR-1) and methanol (CR-2) as solvents and amentoflavone was isolated from both extracts.The CR-2 extract showed the better activity against the parasite, with an IC 50 value of 95.1 ± 5.4 µg/mL and 20.6 ± 1.4 µg/mL against promastigote and amastigote forms, respectively.This extract showed lower cytotoxicity (IC 50 =182.4± 2.3 µg/mL) against peritoneal macrophage from BALB/c mice and a selectivity index of 9. Amentoflavone showed an IC50 of 5.9 ± 0.3 µg/mL against amastigote form and a selectivity index of 9. Results suggest that CR-2 extract and amentoflavone could be explored as new antileishmanial alternatives.