Maclura is a plant genus little known and used, species of which have been mainly used in the recovery of soils, for medicinal purposes such as dental infection treatments, and as wood for making furniture and construction. The overexploitation of this genus has placed certain species in endangered extinction status in some countries, such as Brazil. In addition, the scarce research and information limit the development, cultivation, and management of its species regarding their biochemical composition, which includes bioactive compounds such as the phenolic and flavonoid compounds found in some species such as M. pomifera, M. cochinchinensis, and M. tinctoria. The plants’ antioxidant, antimicrobial, anticancer, anti-inflammatory, and antiproliferative activities have been attributed to these compounds. Other biochemical components such as ashes, insoluble lignin, holocellulose, and the high content of lipids and carbohydrates have been identified to be used to produce biofuels, with characteristics very similar to fuels derived from petroleum. This review aims to analyze the current knowledge on the plant genus Maclura, exploring its biochemical compounds and potential applications, including as a food additive, antioxidant supplement, in agriculture, for therapeutic purposes, aquaculture, and the cosmetic and industrial sector.