Abstract Context: Gentamicin is an antibiotic that is effective against Gram-negative microorganisms. However, its clinical applications are often limited due to nephrotoxic effects. Objective: This study investigated the protective effects of aqueous-ethanol extract of Tamarindus indica L. (Leguminosae) fruits against gentamicin-induced renal toxicity. Materials and methods: A daily dose of 200 mg/kg of 70% aqueous-ethanol extract derived from T. indica was employed in male rabbits as a co-therapy with gentamicin (80 mg/kg) for a period of three weeks. Serum and urinary renal function parameters and histological assessments were carried out and compared with one way analysis of variance (Graphpad prism version 5.00, Graphpad Software, San Diego, CA). Results: The results showed that gentamicin-treated animals had significantly elevated blood urea nitrogen (54.1 ± 2.6 mg/dl), serum creatinine (4.0 ± 0.1 mg/dl), serum uric acid (2.3 ± 0.1 mg/dl) and urinary protein excretion (3.8 ± 0.3 mg/dl) with a fall in body weight (10 ± 1%), creatinine clearance (0.7 ± 0.09 ml/min), serum potassium (3.4 ± 0.1 mEq/l), serum calcium (7.6 ± 0.2 mg/dl), urinary volume (126 ± 9 ml/24 h) and urinary lactate dehydrogenase secretion (103.1 ± 4.2 U/l). However, animals treated by co-therapy with gentamicin and T. indica had significantly improved renal structure and function. Discussion and conclusion: Co-therapy of 200 mg/kg/d of T. indica for a period of three weeks successfully prevented functional and morphological derangements caused by gentamicin as assessed by different renal function parameters and histological examinations.