Medicinal plant use plays an important role in the healthcare of many South Africans. Furthermore, in orthodox medicine, conventional antimicrobial agents are amongst themost commonly prescribed groups of drugs. Therefore, due to the prevalence of use of these two forms of healthcare, there is a high probability for their concurrent use. Thus, the aimof this study was to evaluate the interactive antimicrobial and toxicity profiles of six Southern African medicinal plants (Agathosma betulina, Aloe ferox, Artemisia afra, Lippia javanica, Pelargonium sidoides and Sutherlandia frutescens) when combined with seven conventional antimicrobials (ciprofloxacin, erythromycin, gentamicin, penicillin G, tetracycline, amphotericin B and nystatin). Antimicrobial activity was assessed using the minimum inhibitory concentration (MIC) assay against a range of pathogens and interactions were further classified using the sum of the fractional inhibitory concentration (SFIC). Notable synergistic or antagonistic interactions were studied at various ratios (isobolograms). The toxicity of the individual samples, aswell as the notable combinations, was assessed using the brine-shrimp lethality assay (BSLA) and the 3-(4,5 dimethylthiazol- 2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay on the HEK-293 human cell line. Of the 420 antimicrobial: plant combinations studied, 14.29% showed synergistic interactions, 7.56% antagonistic, 35.71% additive and 42.44% indifferent interactions. Some notable synergistic interactions (ciprofloxacin with A. betulina and S. frutescens against Escherichia coli) and antagonistic interactions (ciprofloxacin with A. afra organic extract against Escherichia coli) were identified. None of the notable combinations were found to show toxicity in the BSLA or MTT assay. In conclusion, the majority of combinations were found to have no notable interaction, alleviating some concern related to the concurrent use of these two forms of healthcare.