This study investigated the effect of different supplements of Zn on the growth performance, antioxidant, lipid metabolism, and element deposition of hybrid grouper (♀ Epinephelus fuscoguttatus × ♂ E. lanceolatus). A total of 180 juvenile groupers (bodyweight
10.02
±
0.01
g) were divided into three groups of 20 fish each and fed with ZnSO4, nanozinc oxide (Nano-ZnO), and dihydromyricetin-Zn (DMY-Zn) for 8 weeks(the content of Zn were 123,122.11, and 120.72 mg/kg). The findings revealed that DMY-Zn had a substantial impact on growth, feed conversion ratio, and protein efficiency ratio, whereas Nano-ZnO had a significant impact on feed conversion ratio and protein efficiency ratio. Furthermore, DMY-Zn had a positive effect on the high-density lipoprotein (HDL) content and significantly upregulated the lipid synthesis gene expression (FASN and ACACA) in the liver. The fish fed DMY-Zn had larger levels of catalase (CAT) in both the serum and liver, as well as Cu/Zn-superoxide dismutase (SOD) enzymes in muscle. In terms of antioxidant-related gene expression, the DMY-Zn treatment upregulated the expression of SOD1, Keap1b, and Mt2. Moreover, DMY-Zn also had a prominent effect on element deposition, increasing the concentration of Fe and Zn in the fish liver and muscle and Cu only in the fish muscle. The results revealed that a fish-fed diet enriched with DMY-Zn had significantly higher antioxidant and lipid metabolism activities than a ZnSO4-fed diet. In conclusion, dietary DMY-Zn treatment appears to be effective in increasing hybrid grouper growth, element deposition, antioxidant activity, and lipid metabolism.