Industrialisation, urbanisation, intensive population growth and the need to improve the quality of life are causing an increasing demand for the use of pesticides and plastics. The risk assessment of the impact of xenobiotics on the environment is mainly focused on the analysis of the effect of pure substances, and less on their mixtures, although mixtures are most often present in the environment. The problem with mixtures is the possibility of synergism. In this paper, the ecotoxicity of standard solutions of acetamiprid, clothianidin, thiacloprid and microplastics (shredded plastic bottles (PET) and bottle cap (PP)) and their binary and ternary mixtures was tested. Ecotoxicity was tested according to the standard method ISO 6341:2012 using crusracean Daphnia magna and the standard method ISO 11348-3:2007 using the luminescent bacterium Vibrio fischeri. Chromatographic HPLC-DAD analysis of samples was also performed. The same growth trend of the toxicity curve was observed in all tested xenobiotics. The inhibition of the tested organisms increases with increasing concentration of solutions. In the experiment with Daphnia magna, clothianidin (I = 90%) proved to be the most toxic, followed by acetamiprid and thiacloprid (I = 85%) and microplastics (I = 10%). The mixture of microplastics and thiacloprid showed a synergistic effect between the components, while the other mixtures of microplastics and pesticides showed an antagonistic effect between the components. In the experiment with Vibrio fischeri, acetamiprid (I = 88.28%) proved to be the most toxic, followed by thiacloprid (I = 51.22%) and microplastics (I = 0.5%). Clothianidin did not cause bacterial culture inhibition. All binary mixtures of pesticides and microplastics and binary mixture of pesticides showed a synergistic effect between the components. Only a mixture of acetamiprid and thiacloprid and a ternary mixture of pesticides showed an antagonistic effect among the components. Chromatographic HPLC-DAD analysis revealed the release of the new microplastic compound into the aqueous medium. It is important to emphasize that further research on the synergistic effect of mixtures is necessary in order to better assess their impact on the ecosystem.