Lead (Pb) has been identified as a hazardous heavy metal and a pollutant in the environment, especially due to its human activity. It poisons several physiological systems, such as the hepatic, renal, reproductive, as well as nervous systems, because of an elevation in oxidative damage caused by the formation of reactive oxygen species (ROS). Cranberry is a powerful antioxidant in addition to being a component of an anti-inflammatory disease treatments. The goal of this study was to see if cranberry extract could protect rats from toxicity caused by lead acetate. Addition of cranberry extract at a dose of 75 and 150 mg/kg to rats allowed to treat with lead acetate at a dose of 50 mg/kg to 6 weeks significantly protected the rats from the lead acetate-induced increase in both serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenases (LDH), total and direct bilirubin, alkaline phosphatase (ALP), creatinine, urea, total cholesterol (TC), triglycerides (TG), LDL-C and VLDL-C in addition against an elevation of serum glucose, tumor necrosis factor-alpha (TNF-α) and malondialdehyde (MDA).Treatment with cranberry extract at a dose of 75 and 150 mg/kg also led to a valuable rise in serum total soluble protein, albumin, globulin, HDL-C, triiodothyronine (T3), total thyroxine (T4) as well as hepatic and renal tissue of reduced glutathione (GSH), superoxide dismutase (SOD), catalase activity (CAT) and total antioxidant capacity (TAC) as compared to lead acetate-treated rats. Cranberry has hepato-renal protective impacts in restoring liver and kidney function, according to histopathological evaluation of hepatic and renal tissues. These findings have shown, in conclusion, that cranberry extract has such a strong protective effect in rats suffering from hepato-renal toxicity caused by lead acetate.