The objective of the present work is to find supportive evidence for the use of Caesalpinia bonducella in nephrolithiasis. For safety assessment of ethanolic extract of seed of C. bonducella (ECB), acute and subacute oral toxicity studies was performed. In the acute oral toxicity study at a dose of 2,000 mg/kg and subacute oral toxicity study at dose of 250, 500, and 1,000 mg/kg, no changes were seen in the behavior, haematological parameters, biochemical parameters, histopathology of major organ, and body weight of rats. The efficacy of ECB at dose of 200 and 400 mg/kg was studied in ethylene glycol, glycolic acid, and sodium oxalate induced urolithiasis in rats and marketed cystone tablet at a dose of 750 mg/kg was used as the standard drug. The mean body weight difference, urinary parameters (urine pH, urine volume, levels of calcium, magnesium, and phosphorus), and serum biochemical parameters [urea, Blood urea nitrogen (BUN), creatinine, uric acid, and alkaline phosphatase] were measured. Urolithiasis caused a significant decrease in mean body weight, pH, and volume of urine and increased in both serum biochemical parameters and urinary electrolyte concentration as compared with the normal control group. Histopathology of kidneys were showed increased glomerular hypercellularity, hydropic tubular degeneration, and cast in the induced control group. Ethanolic Extract of Caesalpinia bonducella (ECB) was found to be effective to normalise the above all changes. It was concluded that the ECB was effective in the prevention and elimination of calcium oxalate crystal deposition into kidneys.