This study was conducted to evaluate the total phenolic compounds, the antioxidant properties, and the hepatorenoprotective potential of Calendula officinalis extract against aflatoxins (AFs-) induced liver damage. Six groups of male Sprague-Dawley rats were treated for 6 weeks included the control; the group fed AFs-contaminated diet (2.5 mg/kg diet); the groups treated orally with Calendula extract at low (CA1) and high (CA2) doses (500 and 1000 mg/kg b.w); the groups treated orally with CA1 and CA2 one week before and during AFs treatment for other five weeks. The results showed that the ethanol extract contained higher phenolic compounds and posses higher 1,1-diphenyl 1-2-picryl hydrazyl (DPPH) radical scavenging activity than the aqueous extract. Animals fed AFs-contaminated diet showed significant disturbances in serum biochemical parameters, inflammatory cytokines, and the histological and histochemical pictures of the liver accompanied by a significant increase in malondialdehyde (MDA) and a significant decrease in superoxide dismutase (SOD) and glutathione peroxidase (GPx) in liver. Calendula extract succeeded to improve the biochemical parameters, inflammatory cytokines, decreased the oxidative stress, and improved the histological pictures in the liver of rats fed AFs-contaminated diet in a dose-dependent manner. It could be concluded that Calendula extract has potential hepatoprotective effects against AFs due to its antioxidant properties and radical scavenging activity.