Objective：To investigate the effect of bisphenol S（BPS）exposure on the homeostasis of neurotransmitter metabolism in the mice brain-gut-microbiota axis. Methods：A subchronic BPS exposure model using male C57BL/6J mice was established. The neurotransmitters in tryptophan and tyrosine pathways in the prefrontal cortex，serum and intestine were detected with UHPLC-MS/MS. The gut microbiota analysis was detected based on 16S rRNA gene sequencing. Results：BPS exposure resulted in neurotransmitter metabolism disorders of tryptophan and tyrosine pathways in the mice prefrontal cortex，serum and intestine. In the tryptophan pathway，when compared with the control group，5-HT was decreased in the prefrontal cortex（PFC），serum and intestine of the BPS-exposed group，while 3-HK was greatly increased in the PFC and serum. In the tyrosine pathway，BPS exposure significantly increased L-dopa and DA levels in the PFC，but decreased the counterparts in the intestine. Additionally，BPS exposure led to a differential distribution of gut microbiota in BPS-exposure mice. In the genus level，the Acinetobacter，Lactobacillus and an unclassified_Clostridiales exerted great differences between the two groups. Conclusion：BPS exposure can affect central and peripheral neurotransmitter metabolism in tryptophan pathway and tyrosine pathway through the brain-gut axis. Additionally，BPS exposure caused gut microbiota disturbance.