Food waste is a serious problem with negative environmental and economic consequences. Unused food (either as waste or by-products and referred to as food residues in the present work) is a source of carbohydrates, lipids, proteins, vitamins, minerals and bioactive compounds that could be used in an alternate or secondary life cycle to avoid discarding it. The present work reviews the potential use of food residues for the bioengineering of single-cell protein (SCP), addressing aspects of production, nutrition and safety, as well as the main challenges and perspectives. SCP is obtained from various microorganisms, including fungi, bacteria, yeasts and algae, in pure or mixed form. SCP generally contains a higher percentage of protein (30–80%) compared to soy (38.6%), fish (17.8%), meat (21.2%) and whole milk (3.28%). SCP is a source of essential amino acids, including methionine, threonine and lysine. The use of food residues as substrates for the production of SCP would reduce production costs (35–75%); however, optimization and industrial scaling are some of the main challenges to its sustainable production. The use food waste and agro by-products from the food industry could be a promising alternative to obtain protein according to a circular production scheme.