Microplastics (MPs), an emerging group of pollutants, not only have direct toxic effects on aquatic organisms but also cause combined toxicity by absorbing other pollutants. Triphenyltin (TPT), one of the most widely used organotin compounds, has adverse effects on aquatic organisms. However, little is known about the combined toxicity of MPs and TPT to aquatic organisms. To investigate the individual and combined toxicity of MPs and TPT, we selected the common carp (Cyprinus carpio) for a 42-day exposure experiment. Based on the environmental concentrations in a heavily polluted area, the experimental concentrations of MPs and TPT were set at 0.5 mg L-1 and 1 μg L-1, respectively. The effects of MPs combined with TPT on the carp gut-brain axis were evaluated by detecting gut physiology and biochemical parameters, gut microbial 16S rRNA, and brain transcriptome sequencing. Our results suggest that a single TPT caused lipid metabolism disorder and a single MP induced immunosuppression in carp. When MPs were combined with TPT, the involvement of TPT amplified the immunotoxic effect induced by MPs. In this study, we also explored the gut-brain axis relationship of carp immunosuppression, providing new insights for assessing the combined toxicity of MPs and TPT. At the same time, our study provides a theoretical basis for evaluating the coexistence risk of MPs and TPT in the aquatic environment.