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Leishmaniasis is a group of protozoan parasitic diseases caused by various Leishmania species. The clinical manifestations range from skin abrasions to lethal infection in the visceral organs such as the liver and spleen. The emergence of drug resistance, long hospitalization periods, and various adverse effects of the current therapeutic regimen have incited the quest for exploring novel molecules as efficient treatment regimens. Eugenol is the major component of clove essential oil and has significant biological potential with anti-microbial properties. Moreover, natural product derivatives having the isoxazoline group have shown promising pharmacological applications. Thus, various analogs were synthesized and characterized to explore the anti-leishmanial potency of eugenol and isoxazoline hybrid. Results from the in vitro assay against Leishmania donovani parasites identified three potent derivatives (7e, 8a …