Continuous exposure to sodium fluoride (NaF) imbalances the oxidative status in the body. The current study investigated the effect of the selenium/chitosan-folic (Se/chitosan-folic acid) novel metal complex on oxidative injury and tissue damage in the hepatic tissues of male rats exposed to (NaF). Male rats received NaF (10.3 mg/kg) and Se/chitosan-folic acid (0.5 mg/Kg) orally for successive 30 days. Male rats exposed to NaF showed multi-histopathological alterations in the hepatic tissues including degenerative changes. NaF exposure elevated hepatic oxidative stress markers, lipid peroxidation, and lowered the antioxidant defense enzymes. Se/chitosan-folic acid novel complex supplementation significantly prevented hepatic injury, suppressed reactive oxygen species (ROS) generation and lipid peroxidation, and enhanced the antioxidant defense enzymes. In addition, Se/chitosan-folic acid supplementation improved the hepatic tissues of NaF-exposed male rats. In conclusion, the Se/chitosan-folic acid novel metal complex protects against NaF-induced oxidative injury and tissue injury in the hepatic tissues of male rats. The Se/chitosan-folic acid novel metal complex upregulated the hepatic tissues and enhanced the antioxidant defense enzymes in male rats.