Aspidosperma excelsum Benth. (Apocynaceae) is an Amazonian medicinal species traditionally used for treating malaria, inflammatory disorders, liver diseases, fever, and other health conditions. Despite growing scientific interest, knowledge regarding this species remains fragmented and complicated by taxonomic inconsistencies involving botanical synonyms. The present review critically compiled and integrated the available evidence regarding A. excelsum and its validated synonyms, emphasizing taxonomic aspects, ethnomedicinal applications, phytochemical composition, and pharmacological potential. Taxonomic standardization was performed using the Plants of the World Online database, and systematic literature searches identified 45 eligible studies after applying explicit search and eligibility criteria. Ethnobotanical evidence highlighted the widespread traditional use of stem bark preparations, particularly for malaria treatment across Amazonian communities. Phytochemical investigations revealed a remarkable diversity of indole alkaloids, alongside flavonoids, tannins, and terpenoids, reinforcing the species as a promising source of bioactive metabolites. Experimental studies demonstrated antiplasmodial, anti-inflammatory, antimicrobial, antioxidant, antileishmanial, and selective cytotoxic activities, partially supporting traditional therapeutic indications and suggesting convergence between ethnomedicinal knowledge and pharmacological evidence. However, most findings derive from in vitro and preclinical studies. This review consolidates fragmented information, addresses nomenclatural inconsistencies, and establishes a framework to guide future pharmacological investigations.