Prosopis is a commercially important plant genus, which has been used since ancient times, particularly for medicinal purposes. Traditionally, Paste, gum, and smoke from leaves and pods are applied for anticancer, antidiabetic, anti-inflammatory, and antimicrobial purposes. Components of Prosopis such as flavonoids, tannins, alkaloids, quinones, or phenolic compounds demonstrate potentials in various biofunctions, such as analgesic, anthelmintic, antibiotic, antiemetic, microbial antioxidant, antimalarial, antiprotozoal, antipustule, and antiulcer activities; enhancement of H, K, ATPases; oral disinfection; and probiotic and nutritional effects; as well as in other biopharmaceutical applications, such as binding abilities for tablet production. The compound juliflorine provides a cure in Alzheimer disease by inhibiting acetylcholine esterase at cholinergic brain synapses. Some indirect medicinal applications of Prosopis spp. are indicated, including antimosquito larvicidal activity, chemical synthesis by associated fungal or bacterial symbionts, cyanobacterial degradation products, "mesquite" honey and pollens with high antioxidant activity, etc. This review will reveal the origins, distribution, folk uses, chemical components, biological functions, and applications of different representatives of Prosopis.