The present study determined the hepatoprotective and antioxidant potential of the extract obtained from Amazon nut residues. The brown walnut shell of Bertholletia excelsa was collected and extracted sequentially for 48 h with different ethanol:water ratios and the dry extract was obtained by the spray dryer method. Antioxidant activities were evaluated by testing DPPH radicals, ABTS, total phenolics, flavonoids and cellular antioxidant. Subsequently, in vitro and in vivo tests were carried out to evaluate the protective effect of the extract after induction of liver damage with CCL4. Biochemical parameters of liver injury and biochemical markers of oxidative stress and antioxidant capacity were evaluated. In the mass spectrometry study, phenol and organic acids such as protocatechuic acid, gallic acid and citric acid were identified, which contributed to the elimination of free radicals, reducing DPPH and ABTS levels. The cell viability test after treatment with the extract on human fibroblast and human hepatocellular carcinoma cells showed no cytotoxicity. It was observed that the extract inhibited the production of free radicals in human fibroblasts. The dosage of 400 mg/kg was the most effective in reducing serum MDA levels. There was a significant reduction in hepatic biochemical markers in Hepg-2 with the extract tested at concentrations of 100 and 50 µg/mL and in rats there was a reduction after supplementation with the extract at a dose of 400 mg/kg, when subjected to oxidative stress with CCl4. From the results presented, it can be concluded that Bertholletia excelsa residues can be applied preventively against hepatotoxicity through the prevention of oxidative stress.