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ETHNOPHARMACOLOGICAL RELEVANCE The genus Ballota L. (Lamiaceae) comprises 33 to 35 species distributed mainly in temperate and subtropical regions of the world. Some species have been used in folk medicine as antiemetic, antispasmodic, sedative agents, vermifuge, antihemorrhoid and also in treatment of cough, etc. AIM OF THIS REVIEW: This review article aims to provide organized information on the available traditional uses, phytochemical and pharmacological studies of the genus Ballota, and to obtain new insights for further researches. MATERIALS AND METHODS Electronic databases, including Web of Science, Science Direct, Google Scholar, Scopus, PubMed, and Springer Link were used as information sources. General web searches were carried out using Google and Yahoo search engines by applying related search terms. Additional information was derived from books and journals in English, Latin and Persian, and also Ph.D. theses and M.Sc. dissertations. RESULTS Terpenoids (particularly furanolabdane diterpenoids) and flavonoids were the main phytochemical classes identified in the extracts of Ballota species. Furanolabdane diterpenoids, e.g. ballonigrin, dehydrohispanolone, and hispanolone were reported in many species of Ballota. β-Caryophyllene, caryophyllene oxide, and germacrene D were found as the most common major compounds isolated from the essential oils of the genus Ballota. Sixty-four pharmacological studies conducted on cell lines, microorganisms, and animals were included in this review. Some species of Ballota exhibited various pharmacological activities, including promising antidepressant, anxiolytic, sedative-hypnotic, and antitussive activities in animal models. The pharmacological activities can be attributed to bioactive phytochemicals. CONCLUSION The genus Ballota is a valuable source of bioactive compounds with therapeutic potential in different diseases. Some pharmacological studies showed incomplete methodologies and ambiguous findings. Thus, the research designs of pharmacological studies based on traditional uses of Ballota species are strongly needed in cell lines and animal models. More in vitro and in vivo animal studies are required to confirm the safety, clarification of the effective doses, bioactive compounds, and the mechanisms of actions before future clinical studies.