(-)-Epigallocatechin 3-O-gallate (1), the most abundant flavanol in green tea, has been reported to have antiproliferative effects on Trypanosoma cruzi. The present study reports the effects in vitro and in vivo of 1 on Leishmania amazonensis. L. amazonensis-infected macrophages treated with 1 exhibited a significant reduction of the infection index in a dose-dependent manner, with an IC50 value of 1.6 μM. Oral administration of 1 on L. amazonensis-infected BALB/c mice (30 mg/kg/day) resulted in a decrease in the lesion size and parasite burden, without altering serological markers of toxicity. These data demonstrate the in vitro and in vivo leishmanicidal effects of compound 1.