In present study, we investigated the enantioselective behaviors of the chiral antidepressant venlafaxine and its metabolite O-desmethylvenlafaxine in loath Misgurnus anguillicaudatus (M. anguillicaudatus), as well as effects of microplastic on toxicity, distribution and metabolism through a 40-day co-exposure. The contents of SOD and MDA in loach liver elevated when the loach was exposed to venlafaxine and O-desmethylvenlafaxine. Moreover, co-exposure with microplastic might lead to more adverse effect against loach. The distribution of venlafaxine and O-desmethylvenlafaxine were both detected in loath tissues and liver subcellular. The concentrations of venlafaxine and O-desmethylvenlafaxine were lower in water in microplastic-present treatment. Whilst, more contaminants were accumulated in liver through the "vehicle" (microplastic). Enantioselective behavior of venlafaxine and O-desmethylvenlafaxine occurred with R-enantiomers being preferentially degraded. With microplastic present, the bioaccumulation factor (BAF) of venlafaxine and O-desmethylvenlafaxine in loath tissue amplified more than 10 times. In liver subcellular structure, microplastic may help to transport more compounds into subtle areas and postpone the contaminants metabolism in organisms. The present study for the first time gained an insight into the potential ecological effects and environmental behaviors of combined pollutions of chiral pharmaceuticals and microplastic, which could supply important information for environment risk assessment of concurrent organic pollutants and microplastic.