Methicillin-resistant Staphylococcus aureus (MRSA) has been emerging worldwide as one of the most important hospital and community pathogens. Therefore, new agents are needed to treat MRSA associated infections. The present study investigated the antimicrobial activity of ethyl acetate, methanol and water extracts of Curcuma longa L. (C. longa) against MRSA. The ethyl acetate extract of C. longa demonstrated a higher antibacterial activity than the methanol extract or water extract. Since the ethyl acetate extract was more active than the other extracts, the study examined whether the ethyl acetate extract could restore the antibacterial activity of beta-lactams and alter the MRSA invasion of human mucosal fibroblasts (HMFs). In the checkerboard test, the ethyl acetate extract of C. longa markedly lowered the MICs of ampicillin and oxacillin against MRSA. In the bacterial invasion assay, MRSA intracellular invasion was significantly decreased in the presence of 0.125-2 mg/mL of C. longa extract compared with the control group. These results suggest that the ethyl acetate extract of C. longa may have antibacterial activity and the potential to restore the effectiveness of beta-lactams against MRSA, and inhibit the MRSA invasion of HMFs.