Background and Methods: Current therapy against leishmaniasis is unsatisfactory. Efficacious and safe new drugs are needed.In this study, we show the leishmanicidal effect of an essential oil from Chenopodiumambrosioides against Leishmania amazonensis. Results: The tested product had a potent inhibitory action against promastigote and amastigote forms, with 50% effective dose values of 3.7 and 4.6 µg/ml, respectively. The essential oil showed a moderate toxicity on macrophages from BALB/c mice. An optimal dose of 30 mg/kg/day was effective when administered during 15 days by intraperitoneal route to BALB/c mice infected experimentally. Conclusion: These studies revealed a potential source for the discovery of novel drugs to combat the leishmaniasis based on the traditional medicine.