Cactaceae family is well-known for their adaptations to drought and arid environments. This family, formed by four subfamilies (Cactoideae, Opuntioideae, Pereskioideae, and Maihuenioideae) are known for being leafless stem succulent plants with numerous spines, and their commercial fruits, distinguished by their bright colors and their skin covered with bracts. Some of these species have been traditionally used in the food industry (e.g., pitaya, cactus, or prickly pear) or as pharmaceuticals to treat specific diseases due to their active properties. The processing of these fruits leads to different residues, namely pomace, skin, spines, and residues from cladodes; besides from others such as fruits, roots, flowers, mucilage, and seeds. In general, Cactaceae species produce large amounts of mucilage and fiber, although they can be also considered as a source of phenolic compounds (phenolic acids, flavonols and their glycosides), alkaloids (phenethylamines derived betalains), and triterpenoids. Therefore, considering their high content in fiber and fermentable carbohydrates, together with other target bioactive compounds, fermentation is a potential valorization strategy for certain applications such as enzymes and bioactive compounds production or aroma enhancement. This review will comprise the latest information about Cactaceae family, its potential residues, and its potential as a substrate for fermentation to obtain active molecules with application in the food industry.