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Background — Complex polysaccharides have been detected and characterized in Punica granatum or pomegranate constituents who may act as fungal and bacterial inhibitor as well as an anti-inflammatory effect. However, limited studies were reported on using pomegranate extracts as an anti-bacterial mouthwash. Objectives — To determine the effect of Punica granatum (pomegranate) extract on microbial activity of some bacterial genus isolated from the mouth. Material and Methods — This study included preparation of three different concentrations of Punica granatum methanolic extract of 25%, 50%, and 75%. The inhibition activity of these extracts was tested on different strains such as Sm, Sa, Ec, Kp, Sg and Sf. Results — Results exhibited an effective inhibition of pomegranate extracts against most of the tested strains which were isolated from patients' mouths. The 50% and 75% concentrations of methanolic extract exhibited significant inhibition against four tested strains compared to mouthwash (P≤0.05), while the 25% concentration was less effective than the other concentrations and its antibacterial effect was non-significant in comparison with the mouthwash. Conclusions — This study indicates the inhibitory effectiveness of Punica granatum extracts of high percentage on microbial activity of some bacterial genus isolated from patients’ mouths and suggests the possibility prepare a mouthwash from pomegranate extract.