Cirsium setidens is a wild perennial plant species found in Korea that may have anti-oxidative, anti-adipogenic, and hepatoprotective activities. However, details of the toxicology of C. setidens remain unknown. This study was performed to evaluate the toxicological effects of an acute administration and 4-week repeated dosing of a C. setidens extract in Sprague-Dawley rats to ensure the safe use of this extract. C. setidens (1250, 2500, and 5000 mg/kg body weight/day) did not induce significant toxicological changes in groups matched by gender with respect to mortality, clinical signs, body weight, urinalysis, ophthalmoscopy, necropsy findings, hematology, and histopathology. Therefore, this study demonstrates that acute administration and 4-week repeated dosing of C. setidens extract orally using this administration protocol is safe.