Grape pomace (GP) is a winemaking by-product particularly rich in (poly)phenols and dietary fiber, which are the main active compounds responsible for its health-promoting effects. GP-derived products have been proposed to manage cardiovascular risk factors, including endothelial dysfunction, inflammation, hypertension, hyperglycemia, and obesity. Studies on the potential impact of GP on gut health are much more recent. However, it is suggested that, to some extent, this activity of GP as a cardiometabolic health-promoting ingredient would begin in the gastrointestinal tract as GP components (i.e., (poly)phenols and fiber) undergo extensive catabolism, mainly by the action of the intestinal microbiota, that gives rise to low-molecular-weight bioactive compounds that can be absorbed and utilized by the body.