The genus Desmodium includes about 350 species, distributed in tropical and subtropical regions around the world. The objective of this review was to associate the traditional medicinal uses of the genus Desmodium with its biological activities reported in the scientific literature. Traditional medicinal uses and biological activities were described in 56 species. More than 100 traditional medicinal uses have been reported in 43 countries, highlighting the use in inflammatory, gastrointestinal and infectious processes, muscular pain, rheumatic, renal and hepatic affections. Among the 45 biological activities experimentally evaluated, antioxidant, antimicrobial, anti-inflammatory, hepatoprotective and antinociceptive were the most reported. The species with the highest number of studies were D. gangeticum, D. adscendens and D. styracifolium. In conclusion, several traditional medicinal uses have been experimentally supported, demonstrating the pharmacological potential of this genus.