The purpose of this study was to undergo a bio-activity guidedfractionation of four medicinal plants; namely, Neem (Azadirachta indica A. Juss), Ginger (Zingiber officinale Roscoe), Miswak (Salvadorapersica L.) and Lemon (Citrus limonum Risso). The four most active fractions where then used as root canal irrigants, against single species of Enterococcus faecalis, using NaOCl as a positive control.The antimicrobial sensitivity tests in this study included; the Agar well diffusion method (through the observation of the zone of microbialgrowth inhibition diameters), the Minimum Inhibitory Concentration(MIC) test which was determined by micro broth dilution technique todetermine the most effective concentration to be used, and the DirectContact Test, through testing the in-vitro intracanal microbial reduction,using the most potent medicinal plant fractions.The plant extract fractions that exhibited antimicrobial activity againstEnterococcus faecalis as revealed by the agar well diffusion test were;Ethyl acetate fraction of Neem, ethyl acetate, butanol fractions and totalethanolic extract of Ginger, ethyl acetate fraction of Miswak and freshLemon solution. The direct contact test results revealed that (5.25%NaOCl) was associated with less CFU/ml count when compared to thetested plant extracts. Fresh Lemon solution was associated with lessCFU/ml count when compared with all of the tested plant extractsfollowed by butanol fraction of Ginger, ethyl acetate fraction of Miswakand Neem.