L-Carnitine is a unique nutritional supplement for athletes that has been recently studied as a potential treatment for certain renal disorders. However, its efficacy in renal ischemia reperfusion injuries has not been investigated. Rats were randomly assigned to one of five groups (n = 6/group):1, Control negative: received saline, 2,control positive I/R, rats received Sal and ischemia reperfusion at the end of fourth week and 3, L-Car +I/R group: same as Sal and ischemia reperfusion, but rats received L-Car (100 mg∕ kg) intraperitoneally daily for four weeks, 4, metformin +I/R group: same as Sal and ischemia reperfusion, but rats received oral metformin (300 mg/kg/day) daily for four weeks. 5, metformin +I/R group +L-Car: same as group 3, but rats received oral metformin (300 mg/kg/day) daily for four weeks. IR induced a significant increase in serum creatinine, serum K⁺ and serum KIM-1 peaked at 24 hours after I/R. KIM-1 and β -catenin expression is upregulated 168 hours after I/R. L-Car administration led to a significant decrease in serum creatinine in proportional to I/R group, serum K⁺ in proportional to I/R group, and a significant decrease in serum KIM-1 and Kim-1 expression. L-Car administration attenuated I/R-induced increase in oxidative stress marker MDA and increased antioxidant GSH activity. Moreover, the inducer of autophagy (Metformin) led to a significant decrease in serum creatinine, serum K⁺ and a significant decrease in serum Kim-1 and Kim-1 expression in renal tissue. Overall, our results suggest a potential therapeutic role of L-Car and metformin in I/R