Melilotus officinalis (L.) Pall., is traditionally used to treat conditions such as inflammation, edema, bronchitis, kidney stones, menstrual pain, and skin ulcers, and also has been suggested for the treatment of seizures, amnesia, and headaches. In this review, the existing scientific research were presented. PubMed, ScienceDirect, Scopus, EMBASE, Google Scholar, Cochrane, and Iranian databases (Magiran and SID) were searched for phytochemistry, in vitro, animal, and clinical studies conducted on M. officinalis up to May 2025. Data were extracted and summarized, and the methodological quality and risk of bias in clinical studies were assessed. Melilotus officinalis contains a wide range of bioactive compounds, such as coumarins, flavonoids, and phenolic acids, which contribute to its diverse biological properties. These include antimicrobial, antioxidant, anti-inflammatory, antidiabetic, and acetylcholinesterase inhibitory activities. Additionally, the plant shows promising potential for wound healing and anti-aging applications, alongside analgesic, anti-ulcerogenic, antidepressant, and anxiolytic effects. Considering the numerous effects observed in in vitro and animal studies, further clinical investigations on this plant are warranted.