Due to its health benefits, açaí (Euterpe oleracea Mart.), a fruit from the Amazon region, has become an impactful source of studies, which presents the grain as a byproduct. Currently, açaí grains are being used as raw material to make powder after the roasting process to make a hot drink. However, information about the powder and the drink is limited. Thus, this research aimed to evaluate the physicochemical profile of roasted açaí grain samples produced in Brazil and investigate the phenolic compounds and antioxidant (FRAP, DPPH, ABTS e ORAC) activity during in vitro digestion and the cytotoxic/cytoprotective effects in Caco-2 cell culture. Six commercial samples from Brazil's North, Northeast, and Southeast regions were used. The samples were characterized by high carbohydrate content, high acidity, and moisture content by legislation (≤ 5 g/100g). After the in vitro digestion process, all drinks showed higher concentrations of tannins and flavonoids and a greater capacity to absorb oxygen radicals. On the other hand, reduced antioxidant potential against DPPH and ABTS radicals and the action of lowering ferric ions. Geographic regions and the non-standardization of the process influence the chemical composition. The samples produced in the country's North and Northeast showed similarity in the phenolic profile compared to those made in the southeast region. Nineteen phenolic compounds were identified and quantified before and after simulated digestion of beverages made with roasted açaí beans: seven phenolic acids, six flavonoids, three tannins, two simple phenols, and fumaric acid.  They were characterized by chlorogenic acids, vinylic acid, and syringic acid, which are associated with phenolic markers for potential antioxidant activity. All drinks demonstrated low cytotoxicity (> 90%) after the digestive process on the viability of Caco-2 cells. A cytoprotective effect evidence that the samples prevented oxidation, making the product a new beverage of industrial and commercial interest.