Given the fact that carbon quantum dots (CQDs) have been commercially produced in quantities, it is inevitable to make their ways into environment and interact closely with the public. Even though CQDs in the environment have been reported to damage the central nervous system, the underlying mechanisms of neurotoxic effects of CQDs following respiratory exposure is still not clear. Intranasal instilled CQDs, mimicking respiratory exposure, induces neurobehavioral impairments associated with neuronal cell death of ferroptosis and disulfidptosis that is regulated by metabolic reprogramming of glutathione and cysteine pathways in the cortex and hippocampus where CQDs were hardly accumulated. Therefore, further exploration found that dysbiosis in the lung microbiome was found specifically manipulated by CQDs, which correlated with systemic and neuroinflammatory responses, implicating a lung-brain axis other than gut-brain axis as a critical pathway through which microbiota dysbiosis may impact neurological health after respiratory exposure to CQDs. This study pioneers the exploration of the neurological consequences of inhaled CQDs in the environment through the regulation of microbiome-lung-brain axis, which is key in understanding the mechanistic link between CQDs exposure and neurotoxicity. The findings could develop potential strategies for mitigating the neurological effects of CQDs even other types of nanoparticles.