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Abstract: Anadenanthera colubrina var. cebil (Griseb.) is an ecologically adaptable species native to South America, thriving across a variety of ecosystems, including the dry forests and savannas of Brazil, Argentina, Paraguay, and Bolivia, as well as the Andean highlands of Peru and Chile. Beyond its ecological significance, A. colubrina var. cebil is noted for its traditional use in ethnomedicine and for its diverse pharmacological activities reported in the scientific literature. Indigenous communities (Guaraní, Tupí, and Wichi) have long integrated this species into their healthcare and ritual healing practices, using it in ceremonial, medicinal, and shamanic purposes. Applications include the use of plants in psychoactive rituals and in the treatment of respiratory conditions, inflammation, and various infections. The ethnomedicinal diversity associated with A. colubrina var. cebil has been attributed to its phytochemical profile, including alkaloids such as bufotenine (5-hydroxy-N, N-dimethyltryptamine, 5- OH-DMT), N, N-dimethyltryptamine (DMT), and 5-methoxy-N, N-dimethyltryptamine (5-MeODMT), triterpenes, steroids, saponins, and flavonoids (quercetin, anadanthoflavone). Preclinical research has confirmed a wide spectrum of pharmacological properties, particularly in extracts of the bark and leaves. Activities reported include anti-inflammatory, antinociceptive, antimicrobial, antifungal, antioxidant, antidiarrheal, and wound-healing effects. Specifically, bark extracts have shown notable anti-inflammatory effects in rodent paw edema models and in preclinical models of pulmonary emphysema. A. colubrina seed-derived alkaloids are well-documented for their potent psychoactive properties, traditionally employed in ceremonial contexts. However, despite their ethnopharmacological relevance, these compounds can exert significant toxicological effects, with potential cardiotoxic and neurotoxic effects. Conversely, the gum exuded by the plant is composed of high-arabinose heteropolysaccharides, which have been reported to possess significant wound-healing and antidiarrheal potential, while presenting low toxicity and good safety characteristics. This review offers a critical synthesis of the current scientific literature on A. colubrina var. cebil, addressing its ethnobotanical relevance, biogeographical distribution, phytochemical profile, pharmacological activities, and toxicological properties. It is focused on the species’ bioactive potential and identifies current knowledge gaps to guide future research.