Background: Obesity is increasingly taking an important stage as a cause of death worldwide, and interventions with a good cost‐effectiveness ratio are needed. Psychotria densinervia is one of these natural products with health benefits. Objective. The present study evaluated the cytotoxicity, antiadipogenic, low‐density lipoprotein (LDL), oxidation inhibitory activities, and acute toxicity of Psychotria densinervia hydroethanolic leaf and bark extracts.Methods: The cytotoxicity evaluation of the extracts (62.5, 125, 250, and 500 μg/mL) using the MTT assay and the antiadipogenic activity (25, 50, 100, and 200 μg/mL) using oleic acid were carried out in SW‐872 cells. Copper sulfate (CuSO4)‐induced oxidation was used in the evaluation of the effect of extracts (0.25, 0.5, and 1 mg/mL) against LDL oxidation. The oral acute toxicity evaluation of a single dose of 2000 mg/kg of the extracts was performed in Wistar albino rats weighing 127 ± 2 g.Results: The leaf and bark extracts did not show any sign of cytotoxicity at the tested concentrations. The best antiadipogenic activity was observed by the standard orlistat (38.45 ± 1.70 μg/mL), followed by the leaf extract (IC50: 41.47 ± 0.50 μg/mL) and the least the bark extract (IC50: 107.50 ± 0.90 μg/mL). At a concentration of 1 mg/mL, the leaf extract presented an oxidation lag time of 130 min, which was higher and better than that of the bark extract (120 min). Quercetin (standard) presented an oxidation lag time longer than 3 h. The oral acute toxicity evaluation did not show any signs of toxicity indicating that the LD50 was greater than 2000 mg/kg.Conclusion: Based on the results obtained, the P. densinervia hydroethanolic leaf extract possesses a better antioxidant and antiadipogenic activities than the bark extract.