<p><i>Ailanthus excelsa Roxb. (A. excelsa)</i>, a widely used medicinal plant in traditional healthcare systems, has gained attention for its diverse phytochemical composition and therapeutic potential. This review brings together current knowledge on the plant’s bioactive constituents, traditional applications, pharmacological properties, pharmacokinetics, toxicity, and prospective pharmaceutical uses. An extensive literature survey was conducted using reputable databases including PubMed, Web of Science, Scopus, ScienceDirect, and Google Scholar, covering studies from 1960 to 2025. Supplementary insights were gathered from ethnobotanical records, pharmacopoeias, and classical botanical texts. More than 80 natural compounds have been found in different parts of the <i>A. excelsa</i>, like the bark, leaves, roots, and fruits. These compounds belong to several groups such as quassinoids, flavonoids, triterpenes, alkaloids, phenolics, steroids, fatty acids and proteins. Many of these substances have shown important medicinal activities, including the ability to lower blood sugar, fight cancer cells, treat malaria, kill harmful microbes, protect the liver, and reduce inflammation. Traditional uses encompass treatment of respiratory, gastrointestinal, infectious, and metabolic disorders. Although several ethnomedicinal claims have been scientifically substantiated, there is still a lack of comprehensive data on pharmacokinetics, toxicity, dosage optimization, and mechanistic pathways. The findings underscore <i>A. excelsa</i> as a promising candidate for drug discovery and formulation, particularly within advanced delivery systems like nanotechnology. Future interdisciplinary research is essential to fully elucidate its therapeutic potential and ensure its safe, evidence-based integration into modern medicine.</p> Graphical abstract <p>Showing the traditional uses, phytoconstituent, formulation strategy, and pharmacological activity.</p> <p></p>