| Summary: | Schistosomiasis is a tropical disease transmitted in an aqueous environment by cercariae from the <i>Schistosoma</i> genus. This disease affects 200 million people living in risk areas around the world. The control of schistosomiasis is realized by chemotherapy, wastewater sanitation, health education, and mollusk control using molluscicidal agents. This work evaluates the effects of a nanoemulsion containing essential oil from <i>Myrciaria floribunda</i> leaves as a molluscicidal and cercaricidal agent against <i>Biomphalaria glabrata</i> mollusks and <i>Schistosoma mansoni</i> cercariae. The <i>Myrciaria floribunda</i> essential oil from leaves showed nerolidol, β-selinene, 1,8 cineol, and zonarene as major constituents. The formulation study suggested the F3 formulation as the most promising nanoemulsion with polysorbate 20 and sorbitan monooleate 80 (4:1) with 5% (<i>w</i>/<i>w</i>) essential oil as it showed a smaller droplet size of approximately 100 nm with a PDI lower than 0.3 and prominent bluish reflection. Furthermore, this nanoemulsion showed stability after 200 days under refrigeration. The <i>Myrciaria floribunda</i> nanoemulsion showed LC<sub>50</sub> values of 48.11 µg/mL, 29.66 µg/mL, and 47.02 µg/mL in <i>Biomphalaria glabrata</i> embryos, juveniles, and adult mollusks, respectively, after 48 h and 83.88 µg/mL for <i>Schistosoma mansoni</i> cercariae after 2 h. In addition, a survival of 80% was observed in <i>Danio rerio,</i> and the in silico toxicity assay showed lower overall human toxicity potential to the major compounds in the essential oil compared to the reference molluscicide niclosamide. These results suggest that the nanoemulsion of <i>Myrciaria floribunda</i> leaves may be a promising alternative for schistosomiasis control.
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