Introduction: Protection of liver from the aggressive force of various environmental and chemical agents is very important for the overall health of an individual. So, the present study aimed to evaluate the protection efficiency of crude extracts of red radish seeds and roots against paracetamol mediated hepatotoxicity in rats. Methods: Twenty-four male Wistar rats were divided into four groups. Group I was served as normal rats, Group II received orally single dose of 2 g paracetamol/kg body weight on the 22nd day, Group III and Group IV were administered orally with 300 mg/kg/d crude ethanol extract of either seeds or roots of red radish for 21 days, then received paracetamol on 22nd day. After 48 hours of paracetamol administration blood was withdrawn to determine the activities of aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP) and Gama-GT (γ-GT) as well as total and direct bilirubin. Also, liver tissues were separated to determine malondialdehyde (MDA) and nitric oxide (NO) as well as histological changes. Results: Pretreatment of rats with crude ethanol extract of either seeds or roots of red radish significantly (P ≤ 0.05) suppressed the elevations in serum activities of ALT, AST, ALP, γ- GT, total and direct bilirubin as well as liver MDA and NO levels. The results of histopathologic examinations were consistent with the biochemical results. Conclusion: Seeds and roots of red radish have a protection efficiency against paracetamol mediated oxidative damage and hepatotoxicity in rats.