Background: Microemulsion (ME) is a method that has been developed in the recent years for synthesizing the nano-sized drug, metal or non-metal particles. These systems offer various advantages for drug delivery, such as ease of preparation, complete stability, and high drug solvability in many pharmaceutical applications. Objectives: This study aimed at evaluating the protective effect of sour cherry kernel extract microemulsion on methimazoleinduced nephrotoxicity in mice. Methods: Sixty-four male Swiss albino mice were divided to eight groups; each group consisted of eight mice. Group 1 was served as control, received normal saline; group 2 received base of ME without extract for 10 days; group 3 received a single dose of methimazole (100 mg/kg, ip) as positive control only on the 10th day; groups 4 to 6 received ME extract orally in doses of 250, 500, and 1000 mg/kg, respectively, during 10 days and methimazole (100 mg/kg, ip) on the 10th day; group 7 and 8 received ME extract and extract in dose of 1000 mg/kg for 10 days, respectively. Then, on the 11th day, serum samples were collected and used to determine the levels of serum creatinine (Cr) and blood urea nitrogen (BUN). After removing the kidney, malondialdehyde (MDA) and glutathione (GSH) levels and glutathione peroxidase (GPx) and superoxide dismutase (SOD) activity were also determined. Results: The results obtained from the present study indicated a significant increase in the levels of Cr, BUN and MDA, and decrease of GSH, GPx and SOD by methimazole administration. Pre-treatment with ME extract showed reduction in the levels of Cr, BUN, MDA, and increase of GSH, GPx, and SOD. In addition, these observations were confirmed by histopathological changes of the kidney. Conclusions: The current study showed that the extract had a protective effect on methimazole-induced nephrotoxicity and this effect was more for ME extract.