The use of medicinal plants in the treatment of infectious diseases is an acceptable and popular phenomenon in South Africa and worldwide. The potential of extracts from these plants as antimicrobial agents necessitates their scientific evaluation. Therefore, this study evaluated the antimicrobial activity of Carpobrotus edulis; Cotyledon orbiculata; Datura stramonium; Dodonaea angustifolia; and Zanthoxylum capense against Porphyromonas gingivalis; Tannerella forsythensis and Actinobacillus actinomycetemcomitan. Given that most currently used drugs are cytotoxic, the possible cytotoxic effect of these medicinal plants on human periodontal ligaments fibroblasts and human gingival fibroblasts was also determined. The modified broth micro dilution method incorporating resazurin as an indicator of cell growth in 96-well microtitre plates was used to determine the antibacterial activity of the test plants extracts. The extracts showed some significant antibacterialactivity against Porphyromonas gingivalis, Tannerella forsythensis and Actinobacillus actinomycetemcomitans. The activity varied with respect to individual test bacteria. Their minimum inhibitory concentration (MIC) values ranged from 10 to 0.01mg.mr-l. All bacteria tested were inhibited by the highest concentration of the selected plant extracts ( 1 Omg.ml-1). The MTT [3-( 4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide] method was used to determine the cytotoxic effect of test extracts. All extracts tested with the exception of Carpobrotus edulis, inhibited the growth of both human periodontal ligament fibroblasts and human gingival fibroblasts at the tested dilutions, with the cytotoxicity levels being directly related to the concentration of the extracts. The extract of Carpobrotus edulis, inhibited the tested cells at 10-1 for human periodontal ligaments fibroblasts and ≥ 2: 10-2 for human gingival fibroblasts. All other tested concentrations of Carpobrotus edulis extracts enhanced the growth of both human periodontal ligaments and human gingival fibroblasts. The study provided a scientific evidence of the important role that medicinal plants play as antibacterial agents in the treatment of oral infections.