Abstract: Microalgae are rich in bioactive compounds including pigments, proteins, lipids, polyunsaturated fatty acids, carbohydrates, and vitamins. Due to their non-toxic and nutritious characteristics, these are suggested as important food for many aquatic animals. Dunaliella salina is a well-known microalga that accumulates valuable amounts of carotenoids. We investigated whether it could restore the metabolic equilibrium and mitigate the hepatic inflammation induced by zinc oxide nanoparticles (ZnO-NPs) using male zebrafish which were exposed to 1/5th 96 h-LC50 for 4 weeks, followed by dietary supplementation with D. salina at two concentrations (15% and 30%) for 2 weeks. Collectively, ZnO-NPs affected fish appetite, whole body composition, hepatic glycogen and lipid contents, intestinal bacterial and Aeromonas counts, as well as hepatic tumor necrosis factor-  (TNF-). In addition, the mRNA expression of genes related to gluconeogenesis (pck1, gys2, and g6pc3), lipogenesis (srepf1, acaca, fasn, and cd36), and inflammatory response (tnf-a, tnf-b, nf-kb2) were modulated. D. salina reduced the body burden of zinc residues, restored the fish appetite and normal liver architecture, and mitigated the toxic impacts of ZnO-NPs on whole-body composition, intestinal bacteria, energy metabolism, and hepatic inflammatory markers. Our results revealed that the administration of D. salina might be effective in neutralizing the hepatotoxic effects of ZnO-NPs in the zebrafish model.