The reliance on fish meal (FM) as the primary protein source in aquafeeds is becoming increasingly unsustainable due to overfishing and limited resources. Therefore, finding an alternative protein source for FM is a crucial issue in the research of aquafeed nutrition. Corn gluten meal (CGM) is a plant protein source commonly used in aquafeeds that has been considered a practical substitute for FM. This study is designed to evaluate the impacts of substituting FM with CGM in the feed of red sea bream (Pagrus major) on growth, feed utilization, and biochemical composition. Total of 600 juvenile (8.60 +/- 0.011 g; initial mean body weight +/- SE) fish were assigned to twelve 300 L flow-through tanks. The control (Con) diet included 55% FM. In the Con diet, 20%, 40%, and 60% of FM were replaced with CGM, identified as the CG20, CG40, and CG60 diets, respectively. Four isoproteic (51.5%) and isolipidic (14.5%) diets were prepared. All diets were supplied to triplicate groups of fish. Fish were hand-fed to satiation level twice daily for 56 days. At the completion of the 56-day feeding trial, the weight gain (WG) and specific growth rate (SGR) of red sea bream fed the Con and CG20 diets were superior (p < 0.0001 for both) to fish fed the CG40 and CG60 diets. WG and SGR of red sea bream linearly decreased with elevated dietary FM replacement levels (Y = -5.003333X + 38.9667, R-2 = 0.9004, p < 0.0001 and Y = -0.002607X + 0.0314, R-2 = 0.9083, p < 0.0001, respectively). Feed consumption (FC), protein efficiency ratio (PER), and protein retention (PR) of red sea bream fed the Con and CG20 diets were statistically (p < 0.006, p < 0.003, and p < 0.004, respectively) higher than those of fish fed the CG40 and CG60 diets. The feed conversion ratio (FCR) of red sea bream fed the CG40 and CG60 diets were statistically (p < 0.0002) higher than that of fish fed the Con and CG20 diets. The hepatosomatic index (HSI) of fish fed the Con and CG20 diets was statistically (p < 0.005) lower than that of fish fed the CG40 and CG60 diets. Neither the plasma and serum parameters nor the biochemical composition except for arginine and lysine content of the whole-body fish were statistically (p > 0.05) altered by dietary FM substitution with CGM. In conclusion, FM up to 20% could be replaced by CGM in the diet of red sea bream without bringing about negative impacts on the growth, feed utilization, biological indices (except for HSI), blood chemistry, proximate composition, amino acid (AA; except for arginine and lysine content), and fatty acid (FA) profiles.