Due to their peculiar physicochemical properties, nanoparticles (NPs) have the potential to have a detrimental impact on molecular (proteins and nucleic acids), subcellular, cellular, tissue, and organism levels. However, available works on the harmful effects of the water-borne ionizable NPs, such as aluminum oxide nanoparticles (ALNPs) on fish are scarce. Therefore, the toxic impacts of ALNPs on hematological, biochemical, and immunological responses in Nile Tilapia fish were investigated in this work. Additionally, the possible benefits of the promising chamomile essential oil (CEO) as dietary supplement in alleviating such impacts were also targeted. For this, four fish groups were used. The control group received only the basic diet, CEO group (basic diet + 2 mg CEO/kg diet), ALNP group (basic diet with exposure to5.08 mg ALNPs/L water, and ALNPs/CEO group (basal diet + 2 mg CEO/kg diet + 5.08 mg ALNPs/L). Fish exposed to ALNPs showed declines in the growth performance and fish survivability in addition to changes seen in the hematological and protein profiles and stress variables. Along with decreased resistance to the Aeromonas hydrophila challenge, there were also substantial decreases in all humoral immune indicators. In addition to increased mRNA expressions of immune genes in the hepatic tissues. CEO significantly modulated the toxic effects of ALNPs suggesting its utilization as a valuable dietary supplement for fish