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Leishmaniasis belongs to a complex of zoonotic disease caused by protozoa of the genus Leishmania and is considered a major public health problem. Several essential oil chemical components have inhibitory effect against protozoa, including Leishmania donovani. Thus, the aim of this study was to evaluate for the first time the anti-Leishmania activity of two p-menthane monoterpene isomers (EPER-1: perillaldehyde 1,2-epoxide and EPER-2: perillaldehyde 8,9-epoxide) against L. donovani promastigotes as well as evaluating cytotoxic effect on mononuclear peripheral blood cells. Results of anti-Leishmania assay revealed that EPER-2 (IC₅₀ = 3.8 μg.mL⁻¹) was 16-fold more potent than its isomer EPER-1 (IC₅₀ = 64.6 μg.mL⁻¹). In contrast to PBMC cells, EPER-2 was not cytotoxic (IC₅₀ > 400 μg.mL⁻¹) when compared to positive control. These data suggest that the disposition of epoxide group into the p …