This study investigated the in vivo genotoxicity of piquiá pulp (Caryocar villosum) and its potential antigenotoxicity on doxorubicin (DXR)-induced DNA damage by comet assay and micronucleus test. In addition, the phytochemicals present in piquiá pulp were determined. Piquiá fruit pulp (75, 150 or 300 mg/kg b. w.) was administered by gavage to Wistar rats for 14 days, and the animals received an injection of saline or DXR (15 mg/kg b. w., i. p.) 24 h before they were euthanized. The phytochemical analysis revealed the presence of carotenoids; phenolic compounds, including flavonoids; tannins and α-tocopherol in piquiá pulp. No statistically significant differences were observed in the evaluated parameters, demonstrating the absence of cytotoxic and genotoxic effects of piquiá pulp at all tested doses. In liver, kidney, cardiac and bone marrow cells, piquiá significantly reduced the DNA damage induced by DXR. Our results showed that the lowest piquiá dose caused the largest decrease in DNA damage and the highest dose caused the smallest decrease, demonstrating an inverse dose-response of piquiá pulp. Furthermore, we observed a difference in the potential antigenotoxic effects in several tissues. In conclusion, our results demonstrated that piquiá pulp was not genotoxic and inhibited the genotoxicity induced by DXR, but some of the protective effects that were observed depended on the doses and experimental conditions. 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