Background: The nicotine content of cigarettes plays a key role in the pathogenesis of kidney disease. Harmine is a harmal‑ derived alkaloid with antioxidant properties. This study was designed to evaluate the effects of Harmine against nicotine‑ induced damage to the kidneys of mice. Methods: In this study, 64 male mice were randomly assigned to eight groups: saline and nicotine‑ treated groups (2. 5 mg/kg), Harmine groups (5, 10, and 15 mg/kg), and nicotine (2. 5 mg/ kg) + Harmine‑ treated groups (5, 10, and 15 mg/kg). Treatments were administered intraperitoneally daily for 28 days. The weights of the mice and their kidneys, kidney index, glomeruli characteristics, thiobarbituric acid reactive species, antioxidant capacity, kidney function indicators, and serum nitrite oxide levels were investigated. Results: Nicotine administration significantly improved kidney malondialdehyde (MDA) level, blood urea nitrogen (BUN), creatinine, and nitrite oxide levels and decreased glomeruli number and tissue ferric reducing/antioxidant power (FRAP) level compared to the saline group (P < 0. 05). The Harmine and Harmine + nicotine treatments at all doses significantly reduced BUN, kidney MDA level, creatinine, glomerular diameter, and nitrite oxide levels and increased the glomeruli number and tissue FRAP level compared to the nicotine group (P < 0. 05). Conclusions: It seems that Harmine administration improved kidney injury induced by nicotine in mice.