New sustainable ingredients with beneficial properties for health are a main goal for the food industry. In this regard, cocoa shell (CS) and coffee pulp (CP), by-products from the coffee and cocoa industry produced worldwide in large amounts, are suitable candidates. We previously stated these by-products are sources of phytochemicals and dietary fiber with potential hypolipidemic properties. This study aimed to assess the hypolipidemic properties of CS and CP after simulated gastrointestinal digestion. The capacities of the residual fraction of each digestion phase to bind bile salts and cholesterol and inhibit the lipase activity were measured to establish the in vitro hypolipidemic properties of both by-products. Furthermore, the digested fractions effect on lipid accumulation was evaluated in HepG2 cell line. From results, the CS showed higher ability to bind cholesterol (4-24%) and salts (2-3%) in gastric and colonic phases. Meanwhile, during gastrointestinal phase, CP showed a greater capacity to bind cholesterol (1-13%) and bile salts (2%). The capacity to inhibit lipase activity was more accentuated in the CS in gastrointestinal digestion (16%) and in CP during gastric digestion (11%). Likewise, the digested fractions of both by-products (100 µg/mL) significantly alleviated the accumulation of fat (17-20%) in the HepG2 cell model after the stimulation of cells with palmitic acid. This comparative approach suggests that both by-products exhibit similar hypolipidemic properties after in vitro digestion. This study promotes the revalorization of cocoa and coffee by-products as novel ingredients with potential beneficial properties to prevent chronic metabolic diseases due to their remarkable hypolipidemic properties.