Background: The present study was carried out to asses whether mulberry leaves (MLs) have the potential to inhibit the mutagenic effect of cigarette smoke condensates (CSCs). Methods and Results: ML powder was extracted with 70% ethanol, and a yield of 35.1% by weight was obtained. The 70% ethanol extract of ML was further extracted sequentially using diethyl ether, chloroform, butanol, dichloromethane and water. The crude 70% ethanol extract of MLs and its solvent fractions did not show any mutagenic effect when tested at concentrations up to 1 ㎎/ plate against Salmonella typhimurium TA98. In contrast, the crude 70% ethanol extract showed an inhibitory activity against the mutagenicity of CSCs in the presence of S-9 mixture. Among the solvent fractions, the diethyl ether fraction showed the highest inhibitory activity, which increased in a dose-dependent manner, inhibiting mutagenesis by approximately 97.1% at a concentration of 1㎎/plate. Conclusions: In this study, we found that a crude 70% ethanol extract of MLs and the diethyl ether fraction themselves are potentially not mutagenic, but inhibit the mutagenic effect of CSCs.