In the context of human food shortages, the incorporation of non-grain feedstuff in fish feed deserves more research attention. Here, the feasibility and appropriate ratio of non-grain compound protein (NGCP, containing bovine bone meal, dephenolized cottonseed protein, and blood cell meal) for dietary fishmeal (FM) replacement were explored in golden pompano (Trachinotus ovatus). Four isonitrogenous (45%) and isolipidic (12%) diets (Control, 25NGP, 50NGP, and 75NGP) were prepared. Control contained 24% FM, whereas the FM content of 25NGP, 50NGP, and 75NGP was 18%, 12%, and 6%, respectively, representing a 25%, 50%, and 75% replacement of FM in Control by NGCP. Juvenile golden pompano (initial weight: 9.71 ± 0.04 g) were fed the four diets for 65 days in sea cages. There was no significant difference between the 25NGP and Control groups in terms of weight gain, weight gain rate, and specific growth rate; contents of crude protein, crude lipid, moisture, and ash in muscle and whole fish; muscle textural properties including hardness, chewiness, gumminess, tenderness, springiness, and cohesiveness; and serum biochemical indexes including total protein, albumin, blood urea nitrogen, HDL cholesterol, total cholesterol, and triglycerides. However, the golden pompano in 50NGP and 75NGP experienced nutritional stress, and thus some indicators were negatively affected. In addition, compared to the Control group, the expression levels of genes related to protein metabolism (mtor, s6k1, and 4e-bp1) and lipid metabolism (pparγ, fas, srebp1, and acc1) of the 25NGP group showed no significant difference, but the 4e-bp1 and pparγ of the 75NGP group were significantly upregulated and downregulated, respectively (p < 0.05), which may explain the decline in fish growth performance and muscle quality after 75% FM was replaced by NGCP. The results suggest that at least 25% FM of Control can be replaced by NGCP, achieving a dietary FM content of as low as 18%; however, the replacement of more than 50% of the dietary FM negatively affects the growth and muscle quality of golden pompano.