Objective- The purpose of this study was to evaluate the protective impacts of Plantago. major (P. major) against the adverse effects resulted from testicular ischemia/reperfusion (I/R) on kidney and liver.Design- Experimental study.Animals- Twenty-four male rats.Procedures- The testicular I/R was induced by firstly anesthetizing rats using ketamine and xylazine and then, incising the skin of testis region. After the stimulation of testicular I/R by rotating the testis in clockwise direction, fixing for 2 hours and then, re-rotating testis. Then, P. major was administered through intraperitoneal route at the dose of 50 and 100 mg/kg for 14 days. The liver and kidney samples were used for histopathological investigation.Results- It was found that testicular I/R negatively affects the kidney and liver as it was demonstrated in histopathological samples. Degeneration of hepatocytes, necrosis, hyperemia in sinusoids and infiltration of inflammatory cells were found in liver. Similarly, the hyperemia, necrosis, and infiltration of inflammatory cells were observed in the kidney. Administration of P. major diminished significantly these harmful effects with better results at the dose of 100 mg/kg.Conclusion and Clinical Relevance- It is suggested that treatment of rats with P. major is beneficial in terms of reducing the adverse effects of testicular I/R on the kidney and liver tissues and this procedure can be applied in the clinical trials.