In rainbow trout, zinc is among the most important essential micro-minerals involved in many biological processes such as oxidative stress, bone mineralization, and growth. Organic minerals are often reported to be more bioavailable to fish, thus requiring lower amounts to meet the zinc requirement. Rainbow trout are commonly reared as both diploids and triploids, but it is unknown if ploidy status affects how the fish responds to dietary zinc supplementation. This study examined gene expression response patterns in both diploid and triploid rainbow trout fed to satiation for 9 weeks with either inorganic (ZnSO4) or organic (amino acid chelated) zinc supplemented in incremental levels (Zn63, Zn123, Zn183) to an otherwise sufficient basal diet (Zn33). Hepatic expression of genes related to oxidative stress were analyzed and included superoxide dismutase (SOD1; SOD2), glutathione peroxidase (GPX1a; GPX1b1; GPX1b2), catalase (CAT), glutathione reductase (GSR), glutathione S-transferase (GST), liver X receptor (LXR), and the zinc storage protein, metallothionein-A (MTA). Expression of all genes, except MTA, was significantly elevated with organic zinc supplementation (all with a p-value < 0.001). There was also a zinc dose-dependent increase in SOD1 (p = 0.002) and SOD2 (p = 0.020) expression (organic zinc only) and CAT (p < 0.001) expression. Dose-dependent reductions in gene expression were detected for GSR (p < 0.001), GST (p = 0.002), and MTA (p = 0.004). There were also gene expression differences between diploids and triploids, suggesting that triploids were more sensitive to potential improvements in zinc bioavailability in the organic zinc-containing diets. Findings support that zinc supplementation, particularly organic zinc, beyond the dietary requirement may enhance the antioxidant defense system and improve fish health by reducing oxidative stress. However, more research is required for better comprehension of all subsequent effects.