Nephropathies and especially nephrotoxicity have become one of the serious causes of life-threatening conditions because of intensive exposure to xenobiotic whether by environmental pollution or by drug abuse. The present study was undertaken to assess the protective effects of Cinnamomum zeylanicum stem bark aqueous extract (AECZ) on gentamicin-induced nephrotoxicity. AECZ was prepared by maceration in water and tested orally at the doses of 200 and 400 mg/kg/day to prevent gentamicin-induced nephropathies in male Wistar rats. Gentamicin (100 mg/kg/day) was administered for 14 consecutive days by intraperitoneal route, concomitantly with AECZ or silymarin (50 mg/kg/day) used as reference drug. Animal body weight was monitored during the treatment. After the last treatment on the 14th day, animals were sacrificed. Blood was collected for the evaluation of hematological and renal function biomarkers. The homogenate of one kidney was used to assess oxidative stress markers and proinflammatory cytokines, while the other one was fixed in formaldehyde for histopathological studies. Gentamicin decreased body weight, serum total proteins, and calcium level but increased kidneys’ relative weight, serum creatinine, urea, and uric acid. Moreover, the levels of reduced glutathione, catalase, and superoxide dismutase activities were decreased, while an increase in malondialdehyde, proinflammatory cytokines (TNF-α, IL-1β, and IL-6), and nitrites was observed in the negative control group as compared to normal control. Histological analysis of the kidney revealed the presence of tubular necrosis, glomerular degeneration, and macrophage infiltration in the gentamicin-treated group. All these impairment parameters were prevented by AECZ and silymarin treatments. AECZ has a protective effect against gentamicin-induced nephrotoxicity. The antioxidant and anti-inflammatory potentials of this extract may highly contribute to its nephroprotective activity.