The babassu (Attalea speciosa Mart. ex Spreng, syn. Orbignya phalerata Mart), native to Brazil, is valued for its medicinal properties. Babassu mesocarp flour has attracted interest for its high flavonoid content. Given the antioxidant effects of flavonoids-and the potential for pro-oxidant or hepatotoxic effects at high doses, and their interactions with other phytochemicals, this study assessed the toxicity and antioxidant activity of a well- characterized hydroethanolic babassu mesocarp extract following in vitro human gastrointestinal digestion to mimic physiological conditions. Additionally, this study offered a physicochemical characterization of the extract's lipid derivatives. Beyond flavonoids, the crude extract exhibited a complex lipid profile, mainly phytosterols. The digested extract (DBME) showed reduced particle size, and it was not cytotoxic to human liver (HepG2) cells. Strong antioxidant effects were observed in HepG2 under oxidative stress conditions, even at low doses. DBME lowered reactive oxygen species (ROS), restored mitochondrial function, and downregulated ROS-induced antioxidant gene expression, highlighting its protective role against oxidative damage and mitochondrial dysfunction. Our findings reinforce the therapeutic potential of babassu mesocarp extracts as antioxidant agents and support their future consideration as an ingredient in functional foods or dietary supplements, based on the potential synergistic action between flavonoids and phytosterols identified within the same food matrix.