Although β-glucan has diverse benefits for fish health, the potential adverse impacts of excessive supplementation are poorly understood. This study investigated the optimal dosage of β-glucan for coral trout and explored the adverse effects of excessive supplementation. The results revealed that moderate β-glucan supplementation (1) significantly enhanced the weight gain rate and specific growth rate (SGR); (2) significantly improved the intestinal villus length (0.10%), muscle thickness (0.05–0.15%), and α-amylase and chymotrypsin activities (0.05–0.15%); (3) significantly increased liver catalase (CAT), glutathione reductase (GR), alkaline phosphatase, complement 3, immunoglobulin M (IgM), lysozyme, serum superoxide dismutase, CAT, glutathione peroxidase, GR, total antioxidant capacity, acid phosphatase, complement 4, and IgM activities and significantly reduced malondialdehyde contents; (4) upregulated genes in the liver associated with copper-zinc superoxide dismutase (SOD-1), manganese superoxide dismutase (SOD-2), CAT, GSH-Px1a, ACP6, AKP, LZ-c, IgM, C3, and C4-b. However, 0.20% β-glucan significantly inhibited the growth performance of coral trout compared with 0.10% β-glucan. Thus, 0.10% β-glucan represents the optimal dosage for promoting growth, antioxidant activity, and immune responses in coral trout, while higher β-glucan levels weakened these beneficial effects. With an SGR established by a cubic regression analysis, the optimal level of β-glucan for maximal growth of coral trout is 0.082%. This study provides new insights into the health impacts of β-glucan on fish.