This study investigated the effects of the dietary replacing fishmeal (FM) with fermented cottonseed meal (FCSM) on growth performance, body coloration, serum biochemistry, muscle quality, and liver antioxidant capacity of juvenile golden pompano (Trachinotus ovatus). Fish were fed with five experimental diets (0 (FM), 12.5% (CSM12.5), 25% (CSM25), 50% (CSM50), and 100% (CSM100) replacement levels) for 8 weeks. The weight gain rate (WGR), specific growth rate (SGR), and condition factor (CF) in fish fed with CSM25 were significantly higher than those of the FM (P < 0.05). ALT, GLU, TG, TC, and LDL of fish fed with CSM100 diet were significantly higher than those in FM (P < 0.05). No significant difference was observed in SOD, CAT, and MDA among all treatments (P > 0.05). The relative gene expression of Nrf2 of fish fed with CSM25 diet was higher than that of the other groups (P < 0.05). The relative gene expression of Keap-1 of fish fed with CSM25 diet was lower than those in FM (P < 0.05). In addition, the replacement of a high proportion of FM with FCSM negatively affect the liver antioxidant capacity of fish. With dietary replacement of FM with FCSM increasing 0%–25%, the relative expressions of GH, myf5, and MSTN were significantly upregulated (P > 0.05). Based on these results, we recommend that of FCSM in the diet of golden pompano, whereas the optimal level of FCSM should be carefully evaluated. In conclusion, the optimum level of dietary replacing FM with FCSM in T. ovatus diet was 24.74%−29.38% based on SGR and WGR.