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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. <i>Dunaliella salina</i> 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 1/5^th 96 h-LC₅₀ for 4 weeks, followed by dietary supplementation with <i>D. salina</i> 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 <i>Aeromonas</i> counts, as well as hepatic tumor necrosis factor- α (TNF-α). In addition, the mRNA expression of genes related to gluconeogenesis (<i>pck1</i>, <i>gys2</i>, and <i>g6pc3</i>), lipogenesis (<i>srepf1</i>, <i>acaca</i>, <i>fasn</i>, and <i>cd36</i>), and inflammatory response (<i>tnf-α</i>, <i>tnf-β</i>, <i>nf-kb2</i>) were modulated. <i>D. salina</i> 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 <i>D. salina</i> might be effective in neutralizing the hepatotoxic effects of ZnO-NPs in the zebrafish model.