The genus Polygala, the most representative genus of the Polygalaceae family, comprises more than 600 species from all over the world of which around 40 are distributed in China, some of them, being used in the Traditional Chinese Medicine system.We intend to discuss the current knowledge about the traditional uses, and the newest phytochemical and pharmacological achievements with tentative elucidation of the mechanism of action on the genus Polygala covering the period 2013-2019 to provide a scientific support to the traditional uses, and to critically analyze the reported studies to obtain new insights for further researches.The data were systematically collected from the scientific electronic data bases including SciFinder, Scopus, Elsevier, PubMed and Google Scholar.This literature overview reported several traditional uses of different species of Polygala, mainly against wounds, inflammation, cardiovascular and central nervous system disorders. P. altomontana, P caudata, P. flavescens, P. glomerata, P. japonica, P. molluginifolia, P. sibirica, P. tenuifolia are the main species which have been studied in the last few years. Phytochemical studies showed that they contain triterpene saponins, triterpenes, terpenoids, xanthones, flavonoids, coumarins, oligosaccharide esters, styryl benzoic compounds, benzophenones, and polysaccharides. Pharmacological in vitro and in vivo studies and proposal of the mechanisms of action indicated that pure constituents and extracts of Polygala ssp exhibited significant anti-inflammatory, neuroprotective, antiischemic, antidepressant, sedative, analgesic, antiatherosclerosis, antitumor and enzyme inhibitory properties.This review on traditional uses and phytopharmacological potential of the genus Polygala revealed updated insights which can be explored for further mechanism-based pharmacological activities and structure/activity relationships studies and a better comprehension of the development of Chinese medicine preparations. However some pharmacological studies showed several gaps such as incomplete methodologies and ambiguous findings. More high scientific quality preclinical studies with pharmacokinetic considerations will be required in the future to assess the traditional uses of some species of this genus. This might lead to efficacy and safety issues in clinical trials and to potential medicinal applications.