The liver is the most important organ in the body. Hepatocyte oxidative damage occurs to excess ROS. Liver fibrosis is a mechanism that the immune system uses to treat extreme inflammation by repairing damaged tissue with the creation of a scar. The outcome of fibrosis may be reversed by consuming natural plant extracts with high ROS-scavenging ability. The date palm fruits contain caffeic acid, gallic acid, syringic acid, and ferulic acid, which have anti-inflammatory, antioxidant, and hepatoprotective properties. This study aimed to prepare a date fruit extract, load it onto chitosan nanoparticles, and compare its anti-fibrotic activity with the unloaded crude extract in the CCl-mouse model. Our findings show that nanocomposite (Cs@FA/DEx) has anti-fibrotic properties and can improve liver function enzymes and endogenous antioxidant enzymes by inhibiting cell apoptosis caused by CCl-induction in mice. Furthermore, significantly reduced CD95 and ICAM1 levels and down-regulation of TGFβ-1 and collagen-α-1 expression demonstrated the anti-fibrotic effects of the Cs@FA/DEx. Therefore, the Cs@FA/DEx might be an innovative supplement for inhibiting liver fibrosis and hepatocyte inflammation induced by chemical toxins. Besides, this nano-supplement could be a promising anti-hepatocellular carcinoma agent as it has potent in vitro anticancer activity against the HePG2 cell line.