To obtain the coffee beverage, approximately 90% of the edible parts of the coffee cherry are discarded as agricultural waste or by-products (cascara or husk, parchment, mucilage, silverskin and spent coffee grounds). These by-products are a potential source of nutrients and non-nutrient health-promoting compounds, which can be used as a whole ingredient or as an enriched extract of a specific compound. The chemical composition of by-products also determines food safety of the novel ingredients. To ensure the food safety of coffee by-products to be used as novel ingredients for the general consumer population, pesticides, mycotoxins, acrylamide and gluten must be analyzed. According with the priorities proposed by the Food Agriculture Organization of the United Nations (FAO) to maximize the benefit for the environment, society and economy, food waste generation should be avoided in the first place. In this context, the valorization of food waste can be carried out through an integrated bio-refinery approach to produce nutrients and bioactive molecules for pharmaceutical, cosmetic, food and non-food applications. The present research is an updated literature review of the definition of coffee by-products, their composition, safety and those food applications which have been proposed or made commercially available to date based on their chemical composition.