Selenium nanoparticles (SeNPs) have attracted wide attention for their use in nutritional supplements and nanomedicine applications. However, their potential to protect against autoimmune hepatitis has not been fully investigated, and the role of their antioxidant capacity in hepatoprotection is uncertain. In this study, chitosan-stabilized SeNPs (CS-SeNPs) were prepared by means of rapid ultra-filtration, and then their antioxidant ability and free-radical scavenging capacity were evaluated. The hepatoprotective potential of a spray-dried CS-SeNPs powder against autoimmune liver disease was also studied in the concanavalin A (Con A)-induced liver injury mouse model. CS-SeNPs with size of around 60 nm exhibited acceptable oxygen radical absorbance capacity and were able to scavenge DPPH, superoxide anion, and hydroxyl radicals. The CS-SeNPs powder alleviated Con A-caused hepatocyte necrosis and reduced the elevated levels of serum alanine transaminase, aspartate transaminase, and lactic dehydrogenase in Con A-treated mice. These results suggest that the CS-SeNPs powder protected the mice from Con-A-induced oxidative stress in the liver by retarding lipid oxidation and by boosting the activities of superoxide dismutase, glutathione peroxidase, and catalase, partly because of its ability to improve Se retention. In conclusion, SeNPs present potent hepatoprotective potential against Con A-induced liver damage by enhancing the redox state in the liver; therefore, they deserve further development.