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The present study was performed to evaluate the safe dose of ethanolic Eruca sativa leaves extract in healthy adult male rats. Twenty-five male Wister rats were divided into 5 groups: Group I (Control): received no treatment, groups 2, 3, 4, and 5 received 1, 3, 5, and 6 g/kg BW orally per day for 35 days. On the 36 day, rats were euthanized. Body weights were recorded. Serum biochemical analysis and the expression level of liver and kidney p53 and Bcl-2 were determined. Histopathology of liver and kidney, and TNF-α immunohistochemistry were examined. The ethanolic extract revealed the content of phenols, flavonoids, and fatty acids. Determination of biochemical parameters showed no significant difference in the estimated parameters between control and treated groups. While the treated groups did not show any significant changes expressions of p53 and Bcl-2 as observed by histopathological and immunohistochemical examination as compared to the control group, liver and kidney toxicity occurred for the rat groups administered 6g/kg. In conclusion, Eruca sativa is not toxic and there were no structural and functional changes in the liver and kidney when administered the doses of 1–5 g/Kg BW over a 35-day period through its potent antioxidant activity in rats and that toxicity that occurred in the 6g/kg-day group may be caused by a high concentration of glucosinolates.