A microwave-assisted extraction (MAE) procedure has been optimized to simultaneously provide multifunctional extracts ofMenthasp. leaves with improved antioxidant properties and, for the first time, with optimal antimicrobial activity. Among the solvents evaluated, water was selected as the extractant in order to develop a green procedure and also for its improved bioactive properties (higher TPC andStaphylococcus aureusinhibition halo). MAE operating conditions were optimized by means of a 3-level factorial experimental design (100 °C, 14.7 min, 1 g of dry leaves/12 mL of water and 1 extraction cycle), and further applied to the extraction of bioactives from 6 differentMenthaspecies. A comparative LC-Q MS and LC-QToF MS analysis of these MAE extracts was carried out for the first time in a single study, allowing the characterization of up to 40 phenolics and the quantitation of the most abundant. Antioxidant, antimicrobial (Staphylococcus aureus,Escherichia coliandSalmonella typhimurium) and antifungal (Candida albicans) activities of MAE extracts depended on theMenthaspecies considered. In conclusion, the new MAE method developed here is shown as a green and efficient approach to provide multifunctionalMenthasp. extracts with an added value as natural food preservatives.