Eupatorium perfoliatum L., commonly known as boneset, has a long history of use in traditional medicine for treating fever, colds, and inflammation. This review explores the ethno pharmacology, photochemistry, and pharmacology of boneset. Scientific studies have validated some traditional uses by identifying a rich array of chemical constituents, including volatile oils, caffeic acid derivatives, flavonoids, sesquiterpene lactones, tannins, and polysaccharides. These compounds contribute to boneset's therapeutic effects, such as anti-inflammatory, Antioxidative, antiplasmodial, and Immunomodulatory activities. Preclinical studies support the anti-inflammatory properties of ethanolic extracts, aligning with its traditional use. While clinical trials suggest potential benefits for common colds, methodological limitations necessitate more rigorous research. Ensuring consistent quality and efficacy requires robust analytical methods and pharmacopoeial standards. Bridging the gap between historical use and modern science is crucial for maximizing the therapeutic potential of Eupatorium perfoliatum L.