This study investigates the impact of prolonged cyclic hypoxia on the health of Nile tilapia (Oreochromis niloticus), focusing on behavior, brain oxidative stress, neurotransmitters and inflammatory responses over four weeks, as well as the microarchitectural integrity of brain tissue. Furthermore, the potential protective role of camel whey protein hydrolysate (WPHC, 75 g/kg diet) was examined. Fish were fed a basal diet or a diet replaced with 75 g/kg WPHC, according to the experimental protocol, we assigned four groups; the control (normoxic group), WPHC group (fed the camel whey protein-replaced diet in normoxic conditions), a hypoxia group (cyclic hypoxia), and a hypoxia + WPHC (fed the camel whey protein-replaced diet in hypoxic conditions). The results indicated that cyclic hypoxia significantly impaired ingestive behaviour and swimming activity. Biochemically, it induced oxidative stress, as evidenced by reduced levels of glutathione (GSH), superoxide dismutase (SOD), and catalase (CAT), alongside an increase in malondialdehyde (MDA) in brain tissue. Moreover, the neurotransmitter analysis revealed a marked decline in dopamine (DA) and serotonin (5HT) levels in hypoxic groups compared to normoxic. At the molecular level, there was a notable upregulation of hypoxia-inducible factor alpha (hif-α), fabp-4, pro-inflammatory, and pro-apoptotic genes in response to cyclic hypoxia. Remarkably, fish fed with WPHC-replaced diets showed substantial improvements across behavioral, biochemical, and molecular levels. WPHC also demonstrated a restorative effect on the brain’s microarchitecture, mitigating the adverse effects of hypoxia. These findings suggest that WPHC is a valuable alternative protein source in aquaculture to mitigate the neurobehavioural alterations induced by cyclic hypoxia stress, enhancing the accommodation of O. niloticus to this stress through multiple biological pathways. The study underscores the potential of WPHC in promoting sustainable aquaculture practices, particularly in environments disposed to hypoxic stress.