A 60-day feeding trial was performed to optimize dietary protein based on the ideal protein concept for genetically improved farmed tilapia (GIFT) juveniles reared in inland saline water (ISW) of 10 ppt salinity. Seven heteronitrogenous (373.6–256.5 g crude protein/kg), isocaloric (∼ 16 MJ digestible energy/kg) and isolipidic (∼ 80 g lipid/kg) semi-purified feeds were formulated and prepared with decreasing levels of crude protein (CP), namely 373.6 (CP1), 352.2 (CP2), 334.5 (CP3), 314.9 (CP4), 293.7 (CP5), 275.2 (CP6) and 256.5 g/kg (CP7). The proportion of total essential and semi-essential amino acids was kept constant in all diets as ideal amino acid profiles and total non-essential amino acids were reduced linearly to reduce the dietary CP levels. Three hundred fifteen juveniles (average weight 4.76 ± 0.01 g) were randomly assigned into seven groups in triplicate. Fish of various groups were fed thrice daily at an apparent satiation level. The growth of juveniles increased linearly and quadratically (p<0.05) when the CP level of diets was decreased from 373.6 (CP1) to 334.5 g/kg (CP3), then declined linearly. The CP2 and CP3 groups had significantly higher feed intake and lower feed conversion ratio. In contrast, low CP-fed groups had superior protein utilization, viscerosomatic index and hepatosomatic index than other groups. The CP1 and CP2 groups had significantly higher whole-body protein and lower lipid content. The whole-body non-essential amino acid content diminished linearly (p<0.05) as dietary CP levels were decreased; the whole-body essential amino acid content remained unchanged (p>0.05). The high CP-fed juveniles (CP1 and CP2) showed a significantly (p<0.05) elevated protease activity, whereas the opposite trend was noticed for amylase activity. The aminotransferase activities of the liver and muscle were reduced linearly (p<0.05) with reduced dietary CP levels. Serum glucose and cholesterol contents elevated linearly (p<0.05) with decreased dietary CP levels. Whereas, the hemoglobin content and RBC count decreased (p<0.05) in the high CP-fed juveniles. The second-order polynomial regression analysis revealed that the optimal dietary CP levels could range from 311.1 to 318.0 g/kg for GIFT juveniles reared in ISW of 10 ppt salinity. Furthermore, by adopting the ideal protein concept, the CP levels in the diet of GIFT juveniles could be reduced from 373.6 to 311.1 g/kg without affecting growth performance. The outcome of this study will assist in developing a low-protein feed with balanced essential amino acids for GIFT culture in ISW.