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Abstract The lignoid fraction (LF) of Ocotea fasciculata, which is rich in yangambin and its epimer, epi-yangambin, showed promising activity against Leishmania sp. Subsequently, LF was incorporated into a solid lipid nanoparticle (SLN) in order to increase its pharmacological efficacy and decrease toxicity. In this regard, the present study was carried out to evaluate the cytotoxic and toxicogenetic potential of LF and LF-SLN in mammalian cells in vitro and in vivo. The cytotoxic activity was evaluated in a non-tumor human cell line (GM07492A) and the toxicogenetic potential was assessed in vitro in a Chinese hamster lung fibroblast cell line (V79) and in Swiss mice. LF-SLN showed no cytotoxic effect at the highest concentration tested (5,000 µg/mL), while LF exhibited an IC50 equivalent to 1,047 ± 4.50 µg/mL. The frequencies of micronuclei observed in vitro and in vivo in mammalian cells treated with different concentrations of LF and LF-SLN did not differ significantly from the negative control group. Therefore, LF and LF-SLN did not show genotoxic or cytotoxic effects under the experimental conditions used. These results contribute to the development of a drug for the treatment of leishmaniasis that is more effective and safer for human health.