Methicillin-resistant Staphylococcus aureus (MRSA) is a bacterium responsible for a number of infections in humans that are difficult to treat, and as a result, is a substantial contributor to morbidity and mortality. In the present study, in search of natural products capable of inhibiting this multidrug-resistant bacterium, we investigated the antimicrobial activity of Lysimachia clethroides Duby root. The antibacterial activities of EtOH extract of Lysimachia clethroides Duby root and its n-hexane, EtOAc, n-BuOH and water fractions were evaluated against 15 strains of methicillin-resistant staphylococcus aureus (MRSA) and 1 standard methicillin-susceptible S. aureus (MSSA) strain by using the minimal inhibitory concentrations (MICs) assay, colorimetric assay using MTT test, checkerboard dilution test. Antimicrobial activity of n-hexane fraction of Lysimachia clethroides Duby root was remarkable. Against the 16 strains, the minimum inhibitory concentrations (MICs) were in the range of 31.25–62.5 ㎍/㎖ and FICI values for n-hexane fraction of Lysimachia clethroides Duby root+AM and n-hexane fraction of Lysimachia clethroides Duby root+OX were checkerboard method performed using the MRSA, MSSA and one clinical isolate strains via MICI 0.12-1 and 0.25-0.75, showing the increase of synergistic effect. When combined together, these antibiotic effects were dramatically increased. These effective combinations could be new promising agents in the management of MRSA.