Mentha piperita L. essential oil (EO) is employed for external use as antipruritic, astringent, rubefacient and antiseptic. Several studies demonstrated its significant antiviral, antifungal and antibacterial properties. The aim of this work is the study of the synergistic effects of M. piperita EO with antibacterials and antifungals that are widely available and currently prescribed in therapies against infections. The observed strong synergy may constitute a potential new approach to counter the increasing phenomenon of multidrug resistant bacteria and fungi. In vitro efficacy of the association M. piperita EO/drugs was evaluated against a large panel of Gram-positive and Gram-negative bacteria and yeast strains. The antimicrobial effects were studied by checkerboard microdilution method. The synergistic effect of M. piperita EO with gentamicin resulted in a strong growth inhibition for all the bacterial species under study. The synergistic effect observed for M. piperita EO and antifungals was less pronounced.