Liver and kidney diseases are public health concerns due to ineffectiveness and adverse effects of orthodox therapeutics. Consequently, medicinal plants are becoming attractive as plausible source of protective agents against hepatorenal toxicities. The protective effect of ethanol leaf extract of Acrostichum aureum (ELAA) was examined in a CCl4 rat model of hepato-renal injury. Forty-eight adult male Sprague–Dawley rats were divided into eight treatment groups (n= 6 each). Treatment lasted for 21 days and the groups included: a negative control that received olive oil, a positive control group that received quercetin (10 mg/kg/day), two groups that received ELAA (50 or 100 mg/kg/day) alone, a CCl4 (1 ml/kg twice a week) treated-group and three CCl4-cotreatment groups that received 50 mg/kg/day ELAA or 100 mg/kg/day ELAA or quercetin with CCl4. On the 22nd day, blood was collected and used for evaluation of hepatorenal health markers including alanine aminotransferase (ALT), aspartate aminotransferase (AST), bilirubin, creatinine, urea, total protein, albumin, Na+, and Cl-. Rats were sacrificed and malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione peroxidase (GPx) levels were determined in the liver and kidney after recording their weights. Compared to the negative control, CCl4 caused significant (p< 0.05) increases in organ weight, organo-somatic indices, ALT, AST, bilirubin, and creatinine, while Na+ and Cl-were significantly decreased. Marked elevation of MDA coupled with decreased SOD and GPx activities were also recorded following CCl4 treatment. Supplementation with ELAA reversed the parameters toward control values similarly to quercetin. Suggesting that ethanol extract of Acrostichum aureum ameliorated CCl4-induced hepato-renal injury by counteracting oxidative stress.