Background: Aflatoxin B1 produced by the fungus Asperagillus flavus causes great economic losses and poses health hazards to human and animals through its toxic biological effects on liver, kidney and lungs. The aim of this work was to study the potential protective effect of Cinnamomum zeylanicum, Berberis vulgaris and Ulva lactuca extractson hepatocyte toxicity induced by A. flavus intakein rats. We also investigated the effect of A. flavus and the studied extracts on liver and kidney structure and function and the potential modulation of p53 and ICAM-1 gene expression as well as the liver antioxidant status. Our results showed a damaging effect of A. flavus intake on both liver and kidney as reflected by liver histopathological examination and the impaired liver and kidney functions measured by ALT, AST, Albumin, Urea, creatinine and glucose. Cinnamon and Berberis and Ulva pre-treatment kept these parameters to almost its normal levels compared to the induced unprotected animals. All tested extracts reduced the oxidative stress status and increased the antioxidant status by lowering TBARS and increasing NO levels significantly but had no significant effect on SOD activity. A.flavus intake causeda significant decline in both P53 and ICAM-1 gene expression; however, administration of Cinnamon or Berberis caused a significant increase in expression with Cinnamon causing the highest increase in p53 and Berberiscausing the highest increase in ICAM-1. In conclusion, we recommended the use of cinnamon Zeylanicum or Berberis vulgaris as protective natural antioxidants against hepatocellular aflatoxin induced toxicity.