Abstract: Chayahuita Amerindians are dwelling in north-west Peruvian Amazon. As they live in an endemic area of cutaneous and muco-cutaneous leishmaniasis, they developed a rich pharmacopoeia against those well recognized diseases [1]. Pseudoelephantopus spicatus (B. Juss. ex Aubl.) Rohr ex Gleason (Asteraceae) is one of the most used Chayahuita remedies against cutaneous leishmaniasis. In the course of evaluating those remedies against in vitro axenic amastigotes of Leishmania amazonensis, P. spicatus extract was found to be very active. Bioguided fractionation led to 3 active compounds (8,13-O-diacetyl-piptocarphol (1), 8-O-acetyl-13-O-ethyl-piptocarphol (2) and ursolic acid. Although these compounds had already been identified in other plants of the Vernoniae tribe (P. spicatus tribe) [2,3], none of them had been isolated from this species. 1 and 2 were found to be more active than amphotericin B against the parasite (IC50 for 1: 0.08±0.04µg/mL, 2: 0.14±0.05mg/mL, and 0.38µg/mL for amphotericin B), explaining at least partially the use of P. spicatus based remedies.