Background: Cocoa bean shell (CBS), a main byproduct of cocoa processing, represents a source of components such as polyphenols and methylxanthines, which have been associated with a reduced risk of several diseases. Therefore, CBS has potential application as a food ingredient. Intestinal mucosa is exposed to immune and inflammatory responses triggered by dietary agents, such as oxysterols, which derive from cholesterol oxidation and are pro-oxidant compounds able to affect intestinal function. We aimed at investigating the capability of the Forastero cultivar CBS, added or not added to ice cream, to protect against the intestinal barrier damage induced by a dietary oxysterol mixture. Methods: Composition and antioxidant capacity of in vitro digested CBS and CBS-enriched ice cream were analyzed by high-performance liquid chromatography and 1,1-diphenyl-2-picryl-hydrazyl radical-scavenging assay, respectively. CaCo-2 cells differentiated into enterocyte-like monolayer were incubated with 60 µM oxysterol mixture in the presence of CBS formulations. Results: The oxysterol mixture induced tight junction impairment, interleukin-8 and monocyte chemoattractant protein-1 cell release, and oxidative stress-related nuclear factor erythroid 2 p45-related factor 2 response Nrf2. Both CBSs protected cells from these adverse effects, probably thanks to their high phenolic content. CBS-enriched ice cream showed the highest antioxidant capacity. Theobromine, which is in high concentrations of CBS, was also tested. Although theobromine exerted no effect on Nrf2 expression, its anti-inflammatory cooperating activity in CBS effect cannot be excluded. Conclusions: Our findings suggest that CBS-enriched ice cream may be effective in the prevention of gut integrity damage associated with oxidative/inflammatory reactions.