Cereus hildmannianus (K.) Schum. (syn. C. peruvianus) is a native medicinal plant in the Neotropical region. C. hildmannianus cladodes extracts are used in folk medicine for weight loss, reducing cholesterol, low-density lipoprotein (LDL) levels, as diuretic and cardiotonic, and to treat various diseases, including pulmonary disorders, rheumatism, and in topical treatment for wounds and lithiasis. Fruits and flowers of C. hildmmanianus have high nutritional value. In this review, previous reports on C. hildmannianus (syn. C. peruvianus) concerning its botanical description, geographical distribution, ethnomedicinal use, phytochemistry, in vitro and in vivo pharmacological properties, food benefits and plant biotechnology were summarized. Scientific search engines, including ScienceDirect, Capes Journals Portal, Google Scholar, PubMed, Scielo, and Scifinder, were consulted to gather data on C. hildmannianus. The present review is an up-to-date and comprehensive analysis of phytochemical compounds, ethnomedicinal uses, phytopharmacological activities, and food value of cladodes, flowers, fruits, seeds, and tissue culture from C. hildmannianus. In traditional medicine, C.hildmannianus is used to treat various diseases, including pulmonary disorders, rheumatism, and in topical treatment for wounds and lithiasis. The extracts from the cladodes of C. hildmannianus exhibited numerous in vitro and in vivo pharmacological activities such as gastroprotective, antioxidant, antifungal, ovicidal, hemagglutinating and slimming, and anticancer activity. These extracts' substances belong to different classes of chemical compounds such as fatty acids, polysaccharides, terpenes, alkaloids, phenolic acids, and flavonoids CONCLUSIONS: Ethnomedicinal surveys have indicated the use of C. hildmannianus, an important medicinal plant in South America, for the treatment of various diseases. The ethnobotanical, phytochemical, pharmacological, and ethnomedicinal properties from various morphological parts of the plant of C. hildmannianus were highlighted in this review, which provides information for future studies, commercial exploration and reveals that this plant has a huge potential for pharmaceutical and nutraceutical applications. Copyright © 2020 Elsevier B.V. All rights reserved.