BACKGROUND: Species of the genus Globularia exist in the Mediterranean region spreading upon Macaronesia, northern Europe, and north-eastern Africa. They have valuable biological activities and remarkable phytochemical contents explaining their traditional uses. PURPOSE: This study reviews phytochemical, pharmacological progress, clinical trials, and molecular mechanisms of action of Globularia extracts and isolated compounds. STUDY DESIGN: In this review the systematic approach is used in summarizing and documenting the information related to Globularia extracts with a special focus on the bioactive component that have numerous biological activities and modes of action. METHODS: The relevant information related to the genus Globularia was collected from different databases (SciFinder, Elsevier, PubMed, and Google Scholar) as well as the clinical trials website (https://clinicaltrials.gov/). RESULTS: The genus Globularia consists of 22 species that are used in traditional medicine as laxative, cholagogue, stomachic, purgative, sudorific, antihypertensive, hypoglycemic, carminative, diuretic, and tonic agents. The extracts of these species have biological potentials, for instance, antioxidant, anti-inflammatory, anti-coagulant, anti-diabetes, anti-bacterial, anti-tuberculosis, enzyme inhibitors, wound healing, toxicological, and neuroprotective activity. Among the valuable bioactive phytochemicals are iridoid glycosides, phenylethanoids, and flavonoid glycosides. CONCLUSION: Despite the efforts made in Globularia isolation there is a lack of knowledge of the biological role of the isolated compounds. Also, the traditional uses of Globularia species are not well-explored and the mechanisms of actions are not investigated thus opening new doors for future efforts in this line.