Sipjeondaebo-tang (SDT, Juzen-taiho-to in Japanese), a traditional Korean herbal medicine, is used as a supplemental treatment for the adverse effects of chemotherapy, radiation therapy, and surgical treatment. However, limited information is available about the long-term safety of SDT. Therefore, we evaluated the potential adverse effects of SDT in Sprague-Dawley rats over a period of 13-weeks. The SDT was administered once daily by gavage to male and female rats at dose levels of 0, 250, 500, 1000 and 2000 mg/kg/day for 13 weeks. The SDT treatment did not result in any toxicologically significant changes in mortality, clinical signs, body weights, food and water consumption, ophthalmoscopy, urinalysis, hematology, serum biochemistry, gross findings, organ weights, histopathology, estrus cycle, serum testosterone levels and sperm analysis. We concluded that the 13-week repeated oral administration of SDT did not cause any adverse effects in rats at dose levels of ≤ 2000 mg/kg/day. Under these experimental conditions, the no-observed-adverse-effect level (NOAEL) was more than 2000 mg/kg/day for both genders. Here, we demonstrated the safety of a 13-week repeated oral dose and considered that it is a safe herbal medicine for human consumption.