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Propolis is a complex mixture, produced by bees, mainly Apis mellifera L., to protect the hive against pathogens and intruders, containing resin (about 50%) and other materials (lipophilic material from leaves, mucilage, gum, waxes, about 30%). The remaining part consists of essential oils (about 10%), pollen (about 5%), and other organic substances (about 5%). The organic compounds are represented by flavonoids, terpenoids, phenolic acids, phenolic esters, and sugars in different proportions. The different activities of the propolis like gastroprotective, hepatoprotective, immunomodulatory, wound healing, antidiabetic and antineoplastic are ascribed at these organic compounds and their antioxidant, anti-inflammatory and antimicrobial activities. Therefore, given the multifaceted aspects of propolis, the aims of this project were: • to evaluate the in vitro antimicrobial activity of a characterized propolis extract obtained by a standardization method (M.E.D.®), developed by B Natural s.r.l.; • to perform a clinical trial, evaluating the activity on the symptoms of upper respiratory tract infection (URTI) with a propolis oral spray; • examine the role of propolis on the gut microbiota, with an in vitro approach. The results demonstrated that the standardized propolis extract exerts in vitro antimicrobial activity with a high activity against pathogens strains and no activity against eubiotic strains. In addition, propolis oral spray application reduces the time for remission of symptoms in subjects with mild upper respiratory tract infections and finally, the propolis extract improves the composition and activity of gut microbiota, as demonstrated by the increased production of short chain fatty acids (SCFAs) and the increased number of different eubiotic bacteria strains (through RT-PCR). In conclusion, we can confirm the efficacy and safety of propolis in different fields on human health applications.