The study investigated the therapeutic of methanolic leaves extract Solanum incanum in cupper induced nephro toxicity. Animals were divided into four groups: A Control (maintained on food and water only), B treated with 300 mg/kg S. incanum, C treated with 200 mg/kg CuO, and D treated with 300 mg/kg and then 200 mg/kg CuO. Serum electrolytes (sodium, potassium, chloride) and kidney functional test (urea, creatinine, and erythropoietin) were evaluated using enzyme-linked immunosorbent assay (ELISA). Prepared slides from the kidney were dehydrated using a dry air oven in xylene for 30 minutes and later mounted on the microscope and viewed using oil immersion ×1000 magnification. The result of electrolytes assays showed significant decrease (P<0.05) with sodium, potassium chloride, and bicarbonate concentration between the control groups 138.00 ± 1.85, 6.03 ± 1.05, 101.25 ± 2.71 compared with the group exposed to CuO only 137.00 ± 4.93, 5.68 ± 0.30, 100.00 ± 3.46 (mmoL/L). The kidney function test show no significantly difference between the control group and group exposed to CuO and then treated with S. incanum methanol extract. For histopathological study, there were mild renal tubular degeneration and tubular dilation blue dot in groups exposed to CuO only. Because of the significant therapeutic effect on electrolyte and as well kidney function, S. incanum is a potential source of remedy against CuO poisoning.