The prevalent exposition of metallic nanoparticles (MNPs) to the aquatic medium and their negative influence on human life is one of the major concerns global. Stress mechanization, as a non-specific and pervasive response, involves all physiological systems, particularly the closely interconnected neuroendocrine and immune systems. In this study, which was designed to obtain more data on the biological effects of ulexit, which prevents oxidative DNA damage by protecting against toxicity damage and offers new antioxidant roles. The concomitant use of ulexite (UX, as 18.75 mg/l) as a natural therapeutic agent against exposure to magnetic nanoparticles (Fe3O4-MNPs/0.013 ml/l) on Oncorhynchus mykiss was investigated for 96 h. The brain tissues were taken at the 48th and 96th hours of the trial period, the effects on neurotoxic, pro-inflammatory cytokine genes, antioxidant immune system, DNA and apoptosis mechanisms were analyzed. In the present study, it was determined that AChE activity and BDNF level in the brain tissue decreased over time in the Fe3O4-MNPs group compared to the control, and UX tried to depress this inhibition. While inhibition was determined in antioxidant system biomarkers (SOD, CAT, GPx, and GSH values), an induction was observed in lipid peroxidation indicators (MDA and MPO values) in Fe3O4-MNPs applied group. The same group data showed that TNF-alpha, IL-6, 8-OHdG and caspase-3 levels were increased, but Nrf-2 levels were decreased. The alterations in all biomarkers were found to be significant at the p < 0.05 level. In general, it was determined that Fe3O4-MNPs caused stress in O. mykiss and UX exhibited a positive effect on this stress management.