Carbonate alkalinity stress is a significant issue in aquaculture operations globally. In this trial, a factorial design was used to investigate the effects of alkaline exposure and camel protein hydrolysate (CPH) dietary supplementation on brain tissue histological features, antioxidant status, and the expression of metabolic genes in Nile tilapia, Oreochromis niloticus. One hundred and sixty fish (16.02 ± 0.14 g) were randomly allocated to four groups with four replicate tanks per group. The first two groups were raised in freshwater and fed either a basal diet (control) or a basal diet supplemented with 75 g CPH/kg. The third and fourth groups were reared in alkaline water and fed the above control or supplemented diet. The alkaline treatment induced neurobehavioral alterations and decreased brain total cholesterol, dopamine, and serotonin levels. In addition, the fish exposed to alkalinity displayed reduced antioxidant enzyme activity and elevated malondialdehyde, indicating oxidative stress. The brain expression of fatty acid synthase (FASN) and fatty acid-binding protein-2 (FABP-2) was reduced by exposure to alkaline stress. Circulatory and degenerative changes were recorded in the brain histological features of the alkaline-exposed. The neurobehavioral and brain neurotransmitter level alterations in alkaline water conditions were much reduced in Nile tilapia fed the CPH-supplemented diet. The CPH diet also mitigated oxidative stress and restored some of the brain histological features in the exposed fish. This study shows that the CPH diet helps the fish adapt to alkaline stress conditions.