The suspensions of citrus fruits peel extracts in 0.5% carboxy methyl cellulose (CMC) were evaluated for hepatoprotective activity in albino rats by inducing hepatic injury with a single intraperitoneal injection of lipopolysaccharide (LPS, 100 ng/kg) and D-galactosamine (D-GalN, 130 mg/kg). The extracts of grapefruit and orange peel at an oral dose of 200 mg/kg exhibited a significant prevention of elevated alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP) and lactate dehydrogenase (LDH) activities, as well as alpha fetoprotein (AFP) level in LPS/D-GalN-intoxicated rats. Protein profile and glucose values in the blood were markedly increased in LPS/D-GalN-intoxicated rats that received citrus fruits peel extracts. In addition, the glutathione (GSH) level and superoxide dismutase activity (SOD) activity were strikingly upregulated, but hepatic malondialdehyde (MDA) level was decreased, by the extracts treatment in LPS/D-GalN-intoxicated rats. Normal histological sections supported the hepatotoxic-preventive action of grapefruit and orange peel extracts. In conclusion, grapefruit and orange peel extracts administration successfully attenuated hepatic dysfunction induced by LPS/D-GalN and may have promise as new therapeutic agents for endotoxic shock possibly via the antioxidant, free radical scavenging, anti-inflammatory and membrane stabilizing activities of the components of both extracts.