Anti-methicillin-resistant Staphylococcus aureus (MRSA) activity of ethanolic extracts of four medicinal plants namely Acorus calamus (rhizome) Hemidesmus indicus (stem), Holarrhena antidysenterica (bark), and Plumbago zeylanica (root), were detected with inhibition zone size ranged from 11 to 44 mm and minimum inhibitory concentration (MIC) varied from 0.32 to 3.25 mg/mL. Further, ethyl acetate, acetone and methanol fractions of above plants demonstrated antibacterial activity. The potency of these fractions based on zone of inhibition and MIC value was relatively higher in P. zeylanica (ethylacetate fraction), followed by acetone fractions of H. indicus, A. calamus, and H. antidysenterica. Time kill assay with most promising fractions of these plant extracts, demonstrated concentration-dependent killing of MRSA within 9-12 h of incubation. Interestingly, synergistic interaction among alcoholic extracts and some fractions of above four plants was evident against MRSA. Further, synergistic interaction of these extracts was detected with one or more antibiotics tested (tetracycline, chloramphenicol, ciprofloxacin, cefuroxime and ceftidizime). The findings also validate the traditional uses of above plants against infectious diseases. Phytochemical studies demonstrated flavonoids and phenols as major active constituents. Further investigations are needed to characterize the active principle and its interaction mechanism with antibiotics.