Introduction: Gentamicin (GD) is an aminoglycoside antibiotic that is used to treat infections with gram-negative bacteria. Due to side effects such as nephrotoxicity, its use is limited. The aim of this study was to evaluate the therapeutic effects of methanolic extract extract of Urtica dioica (UD) on GD-induced nephrotoxicity.Materials and Methods: 32 male Wistar rats weighting between 200-250 g were randomly divided into 4 groups (n=8 in each group): 1- control group received no drug orgentamicin, 2- treatment group with GD (100 mg/kg/d) intraperitoneally for 8 days and distilled water (4 ml/kg) by gavage for two days, 3-treatment group with saline intraperitoneally for 8 days and UD extract (200 mg/kg) for two days, and 4 - treatment group with GD (100 mg/kg/d) intraperitoneally for 8 days and UD extract (200 mg/kg) for two days. On the tenth day, after the last administration, the animals were placed in metabolic cages and urine volume was measured gravimetrically. Following this, the animals were anesthetized, and blood pressure and renal artery blood flow were measured. After that, blood sampls were taken from aorta, and the levels of urea, creatinine, sodium, potassium and osmolality were determined in plasma and also urine samples. Finally, the left kidney was maintained in 10% formalin for histological examination and the right kidney was kept in -20oC for biochemical examination of malondialdehyde (MDA) and the ferric reducing ability of plasma (FRAP) (markers of oxidative stress).Results: UD extract significantly inhibited GM-induced enhancement of plasma creatinine, BUN, absolute excretion of sodium, fractional excretion of sodium and potassium, and MDA levels. UD extract also restored GM-induced derecment in creatinine clearance, urine osmolarity, renal blood flow and FRAP levels.Conclusion: This study showed that UD extract likely via the reduction of oxidative stress and anti-inflammatory and vasodilatory effects could improve nephrotoxicity induced by gentamicin.