The poultry industry relies extensively on antibiotics and coccidiostats as essential tools for disease management and productivity enhancement. However, increasing concerns about antimicrobial resistance (AMR) and the toxicological safety of these substances have prompted a deeper examination of their broader impacts on animal and human health. This study investigates the toxicological effects of antibiotics and coccidiostats on the gut-brain axis and microbiota in turkeys, with a particular focus on molecular mechanisms that may influence neurochemical and inflammatory responses. Our findings reveal that enrofloxacin exposure leads to the upregulation of BDNF, suggesting a neuroprotective effect, while monensin treatment significantly increased eEF2 kinase expression, indicative enhanced neuronal activity. In turkeys infected with Avian Pathogenic Escherichia coli (APEC), early administration of doxycycline and monensin significantly upregulated the mTOR/BDNF and Akt/mTOR pathways, along with elevated histamine levels, underscoring their role in inflammatory responses modulation. However, treatments administered at 50 days post-hatch did not significantly alter protein levels, though both enrofloxacin and monensin increased serotonin and dopamine levels, suggesting potential neurotoxicological impacts on mood and cognitive functions. These results highlight the complex interactions between antibiotic use, gut microbiota alterations, and neurochemical pathways, with toxicological implications for environmental pollution and public health. This research provides critical insights into the potential toxic effects of prolonged antibiotic and coccidiostat exposure in poultry production, emphasizing the need for responsible use to mitigate risks to ecosystems and human health.