Byrsonima crassifolia (Malpighiaceae) has been used in traditional medicine for the treatment of some mental-related diseases; however, its specific neuropharmacological activities remain to be defined. The present study evaluates the anxiolytic, anticonvulsant, antidepressant, sedative effects produced by the extracts of Byrsonima crassifolia, and their influence on motor activity in ICR mice. Additionally, we determine the acute toxicity profiles of the Byrsonima crassifolia extracts and the presence of neuroactive constituents. Our results show that the methanolic extract of Byrsonima crassifolia produces a significant (P0.05). Although the main compound of the methanolic extract was identified as quercetin 3-O-xyloside (12 mg/kg), our findings suggest that flavonoids, such as rutin (4.4 mg/kg), quercetin (1.4 mg/kg) and hesperidin (0.7 mg/kg), may be involved in the antidepressant effects. To the best of our knowledge, the present study constitutes the first report on the presence of the flavonoids with neuropharmacological activity rutin and hesperidin in Byrsonima crassifolia. In conclusion, the present results showed that the methanolic extract standardized on flavonoids content of Byrsonima crassifolia possesses potential antidepressant-like effects in the FST in mice, and could be considered as relatively safe toxicologically with no deaths of mice when orally administered at 2000 mg/kg.