| Summary: | We aimed to evaluate the antimicrobial effects of <i>Glycyrrhiza uralensis</i> extract on <i>Streptococcus mutans</i> and <i>Candida albicans</i> and its biocompatibility for dental applications. The antimicrobial activity of the <i>G. uralensis</i> extracts at concentrations of 50, 100, 150, and 200 µg/mL was assessed using agar disk diffusion tests, counting the total number of colony-forming units (CFUs), spectrophotometric growth inhibitory assays, and microbial morphology observations using scanning electron microscopy (SEM; Merin, Carl Zeiss, Oberkochen, Germany). We measured the polyphenol and flavonoid contents of <i>G. uralensis</i> extracts using ultraviolet–visible spectrometry and the cytotoxicity of these extracts using an MTT (3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay. We identified that <i>G. uralensis</i> extracts had significant antimicrobial effects against <i>S. mutans</i> and <i>C. albicans</i>. The optical density of the experimental groups significantly decreased compared with that of the control group. SEM images revealed that the <i>G. uralensis</i> extract affected the morphology and density of <i>S. mutans</i> and <i>C. albicans</i>. The extract concentration of flavonoids, but not polyphenols, increased with increasing concentrations of the <i>G. uralensis</i> extract. Furthermore, cell viabilities were more than 70% for <i>G. uralensis</i> extracts with concentrations of 50 and 100 μg/mL. Naturally derived <i>G. uralensis</i> is biocompatible and exhibits an excellent antimicrobial effect against oral pathogens such as <i>S. mutans</i> and <i>C. albicans</i>. Thus, <i>G. uralensis</i> extracts can be used for the development of oral products that treat and prevent oral diseases.
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