Coffee brew is a widespread beverage in human diet with several recognized health benefits. However, the relationship between the chemical portfolio of molecules present in coffee and their bioactive function is still overlooked. One of the compounds most prevalent in coffee brew are the soluble fibers, composed by arabinogalactans and galactomannans polysaccharides, and melanoidins, which may influence cholesterol metabolism. Arabinogalactans and galactomannans polysaccharides rich fractions as well as coffee extracts were shown to decrease cholesterol bioaccessibility, due to their capacity to sequestrate bile salt. Furthermore, coffee extracts with distinct roasting degrees were shown to affect the bioavailability of a cholesterol through Caco-2 cell line model, decreasing sterol permeability, which was attributed to an increased sterol precipitation and its deposition on the apical epithelial surface. Arabinogalactans and melanoidins rich fractions were also evaluated regarding the outcome of their fermentability. Both fractions decreased the acetate: propionate ratio, which is indicative of a potential HMG-CoA reductase inhibition. Melanoidin rich fraction also show to decrease the conversion of primary to secondary bile salts, the latter known to be more prone to emulsify cholesterol, impacting on cholesterol bioaccessibility and bioavailability. This study demonstrates that coffee exhibits cardioprotective properties, suggesting potential for developing functional food ingredients from coffee extracts to combat cardiovascular diseases, among the leading causes of death globally.