Crescentia cujete is an economical and medicinal plant of wide indigenous uses including hypertension, diarrhea, respiratory ailments, stomach troubles, infertility problems, cancer, and snakebite. Despite these attributes, C. cujete is largely underutilized, notwithstanding the few progresses made to date. Here, we reviewed the available findings on the ethnobotany, phytochemistry, toxicology, and pharmacology, as well as other economic benefits of the plant. The information on the review was gathered from major scientific databases (Google scholar, Scopus, Science Direct, Web of Science, PubMed, Springer, and BioMed Central) using journals, books, and/or chapters, dissertations, and conference proceedings. The review established the antidiabetic, antioxidant, acaricidal, antibacterial, anti-inflammatory, anthelmintic, antivenom, wound healing, neuroprotection, antiangiogenic, and cytotoxic properties from aqueous and organic (particularly ethanol) aerial parts attributed to several secondary metabolites such as flavonoids, alkaloids, saponins, tannins, phenols, cardiac glycosides, phytosterols, reducing sugar, and volatile oils. Economically, the fruit hard outer shell found applications as musical tools, tobacco pipes, bowls, food containers, and bioethanol production. While most of the current studies on C. cujete are mainly from Asia and South America (Philippines, Bangladesh, India, etc.), part of the persistence challenge is lack of comprehensive data on the plant from in vivo pharmacological studies of its already characterized compounds for probable clinical trials toward drug discovery. Consequently, upon this, modern and novel translational studies including the concept of '-omics' are suggested for studies aiming to outfit more comprehensive data on its therapeutic profiles against pathological markers of diseases and to fully explore its economic benefits. © 2021 Fatai Oladunni Balogun and Saheed Sabiu.