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. Our results demonstrated that ZnO-NPs are hepatotoxic in zebrafish, affecting fish appetite and whole-body composition by disrupting carbohydrate and lipid metabolism. ZnO-NPs altered the intestinal bacterial and Aeromonas counts, and hepatic TNF- and modulated the expression of the gluconeogenesis, lipogenesis, and inflammatory related genes. Depending on the biochemical analysis, histopathology, and gene expression studies, we have demonstrated the antidotal activity effect of D. salina against hepatotoxic and metabolic disorders in ZnO-NP-exposed fish. The underlying mechanisms included restoring the glycolipid equilibrium and anti-inflammatory activity through modulation of the NF- B. Thus, D. salina is suggested as a valuable feed additive for fish.