In this study, we investigated the enantioselective environmental behaviors of the chiral antidepressant venlafaxine (VFX) in lab-scale aquatic ecosystems in the presence of microplastics (MPs). To determine the bioaccumulation, distribution, and metabolism as well as the effects of MPs on aquatic ecosystems, water-sediment, water-Lemna.minor (L.minor), water-Misgumus.anguillicaudatus (M.anguillicaudatus), and water-sediment-L.minor-M.anguillicaudatus ecosystems were set up and exposed to venlafaxine and two levels of microplastics over a 90 day period. The removal efficiencies of VFX ranged from 58 to 96% in different ecosystems, and VFX degraded significantly faster in the complex water-sediment-Lminor-M.anguillicaudatus ecosystem with S-enantiomer preferentially enriched. The main metabolite O-desmethylvenlafaxine (O-DVFX) was also observed in ecosystems, displaying similar enantioselectivity. When exposed to 50 mg L-1 of microplastics, the amount of venlafaxine in sediment and loath (M.anguillicaudatus) were significantly higher than that in the 1 mg L-1 micro plastics treatments, and enhanced accumulation of O-DVFX was observed in loath. The present study for the first time assessed the combined effects of venlafaxine and microplastics in simulated aquatic microcosms, which could help gain an insight into the potential ecological impacts of chiral pollutants and microplastic, and evaluate their environment risks more accurately in future.