The cocoa shell is a by-product generated by the cocoa processing industry that could be used as a nutraceutical owing to the significant amounts of bioactive compounds it contains. Nonetheless, determining the biological potential of the cocoa shell by evaluating the bioaccessibility of the phenolics present therein and their potential antioxidant capacity is still necessary. This work aimed to study the bioaccessibility of phenolic compounds present in the flour (CSF) and an aqueous extract (CSE) from cocoa shells through an in vitro simulated digestion and to assess their antioxidant capacity in vitro and by using intestinal and hepatic cell culture models (IEC-6 and HepG2 cells). A simulated in vitro digestion model (INFOGEST) was used to determine the bioaccessibility of phenolic compounds. Total phenolic compounds and in vitro antioxidant activity were measured by the Folin-Ciocalteu and ABTS assays, respectively. Reactive oxygen species (ROS) were evaluated in IEC-6 and HepG2 cells upon stimulation with t-BOOH. Phenolic compounds present in CSE were more bioaccessible than phenolic compounds present in CSF. During digestion, the bioaccessibility of phenolic compounds from CSF fluctuated in the gastric (2.8 mg/g), intestinal phase (7.6 mg/g), and the colonic (5.7 mg/g) phases. Similarly, for the phenolics of CSE, the bioaccessibility increased from 50.6 mg/g (gastric) to 53.4 mg/g (intestinal) and decreased in the colonic phase (37.2 mg/g). The in vitro antioxidant capacity followed a similar behavior, increasing throughout the digestion in CSF (8.8 to 10.6-fold) and CSE (6.0 to 7.4-fold). Digested CSF and CSE were not cytotoxic for IEC-6 and HepG2 cells and protected their viability under oxidative stress conditions (93-100%). t-BOOH-induced ROS were prevented by CSF (72-88 %) and CSE (81-94 %) bioaccessible fractions in both intestinal and hepatic cells. In conclusion, cocoa shells are a source of potentially bioavailable antioxidant phenolic compounds that may protect cells from oxidative stress.