Objective: The aim of this study was to investigate the possible herb-drug interactions between the traditional herbal formula Guibi-tang (GBT; Guipi-tang, Kihi-to) and conventional drugs. Materials and Methods: GBT was orally administered to either male or female Sprague Dawley (SD) rats once daily at doses of 1000, 2000, or 5000 mg/kg/day for 13 weeks. The messenger ribonucleic acid (mRNA) expression of drug-metabolizing enzyme cytochrome P450 isozymes (cytochrome P450s; CYP1A1, 1A2, 2B1/2, 2C11, 2E1, 3A1, 3A2, and 4A1) was analyzed in hepatic tissues by reverse transcription-polymerase chain reaction. Results: Repeated oral administration of GBT did not significantly influence the mRNA expression of hepatic CYP1A1, 1A2, 2B1/2, 2C11, 2E1, 3A1, 3A2, and 4A1 in male rats. By contrast, in female rats, the mRNA expression of hepatic CYP1A2 and 2B1/2 was significantly increased by repeated GBT treatment. Conclusion: Our findings indicate that caution is required in females when GBT is taken concomitantly with conventional drugs metabolized by CYP1A2 or 2B1/2. Our results provide information regarding the safety and effectiveness of GBT for clinical use.