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Background  Medicinal plants have been used in the treatment of various ailments in most developing countries. Oral infections are the most prevalent diseases in man. The Rhus family has been found to have antimicrobial, antimalarial, and anti-inflammatory properties. Few studies have been done on  Rhus vulgaris  Meikle. A study was conducted to determine the effect of  Rhus vulgaris  Meikle stem bark extracts against selected oral pathogenic microorganisms and the safety of the extracts in vitro and in vivo.    Methods  Methanol:dichloromethane (1:1), methanol and aqueous extracts were tested for bacteriostatic and bactericidal effects against Methicillin Resistant  Staphylococcus aureus  (MRSA),  Staphylococcus aureus, Streptococcus mutans  and  Candida albicans . Cytotoxicity of the active extracts was determined using Vero E6 cell lines while safety was evaluated in mice and rats. Phytochemical screening was performed on the methanol extracts. One-way ANOVA and Tukey’s multiple comparisons tests were performed using IBM SPSS statistics 20.0 for antimicrobial assay and acute toxicity testing. One-way ANOVA and Dunnett’s multiple comparison tests were conducted using GraphPad Prism 8.0 for cytotoxicity assay.    Results  Methanol extract of  Rhus vulgaris  showed significant antimicrobial activity against MRSA (12.00 ± 0.00 mm;  p -value of < 0.005; Minimum Inhibitory Concentration of 0.391 mg/ml; Minimum Bactericidal Concentration of 1.563 mg/ml). The extract were not cytotoxic at 100 μg/ml which was the highest tested concentration. In acute dermal irritation testing, the methanol extract resulted in mild irritation with erythema and flaking that cleared within 8 days. There were no observable adverse effects from oral administration of the extracts (acute oral toxicity testing) at concentrations of 50 mg/kg, 300 mg/kg and 2000 mg/kg. Tannins, saponins, flavonoids, terpenoids, glycosides, alkaloids and phenols were detected in the methanol extract.    Conclusions  Antimicrobial activity of  R. vulgaris  extracts supports its traditional use as a toothbrush. Cytotoxicity demonstrated by the extracts as well as the mild skin irritation warrants further study before  R. vulgaris  can be recommended for the development of effective and safe mouthwashes.

Evaluation of the antimicrobial activity and safety of Rhus vulgaris (Anacardiaceae) extracts