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ETHNOPHARMACOLOGICAL RELEVANCE Origanum majorana L., is an aromatic and medicinal plant distributed in different parts of Mediterranean countries. This species is widely used in traditional medicine for the treatment of many diseases such as allergies, hypertension, respiratory infections, diabetes, stomach pain, and intestinal antispasmodic. AIM OF THE REVIEW This work reports previous studies on O. majorana concerning its taxonomy, botanical description, geographical distribution, traditional use, bioactive compounds, toxicology, and biological effects. MATERIALS AND METHODS Different scientific data bases such as Web of Science, Scopus, Wiley Online, SciFinder, Google Scholar, PubMed, ScienceDirect, and SpringerLink were consulted to collect data about O. majorana. The presented data emphasis bioactive compounds, traditional uses, toxicological investigations, and biological activities of O. majorana. RESULTS The findings of this work marked an important correlation between the traditional use of O. majorana as an anti-allergic, antihypertensive, anti-diabetic agent, and its biological effects. Indeed, pharmacological investigations showed that essential oils and extracts from O. majorana exhibit different biological properties, particularly; antibacterial, antifungal, antioxidant, antiparasitic, antidiabetic, anticancer, nephrotoxicity protective, anti-inflammatory, analgesic and anti-pyretic, hepatoprotective, and antimutagenic effects. Toxicological evaluation confirmed the safety and innocuity of this species and supported its medicinal uses. Several bioactive compounds belonging to different chemical family such as terpenoids, flavonoids, and phenolic acids were also identified in O. majorana. CONCLUSIONS The results suggest that the pharmacological properties of O. majorana confirm its traditional uses. Indeed, O. majorana essential oils showed remarkable antimicrobial, antioxidant, anticancer, anti-inflammatory, antimutagenic, nephroprotective, and hepatoprotective activities. However, further investigations regarding the evaluation of molecular mechanisms of identified compounds against human cancer cell lines, inflammatory process, and microbial infections are needed to validate pharmacodynamic targets. The toxicological investigation of O. Majorana confirmed its safety and therefore encouraged pharmacokinetic evaluation tests to validate its bioavailability.