Mass production, constant use, and improper disposal of plastic products are leading to ever-increasing environmental pollution. Larger plastic particles gradually break down in the environment into smaller particles, of which those smaller than 5 mm are called microplastics (MP). The main commercial plastics are stable in the environment and cannot be biodegraded, but a number of microbial strains have been identified that have the potential to biodegrade MP in the natural environment. Microorganisms such as bacteria, fungi or algae are found everywhere in nature and are able to adapt to different environmental conditions, so it is not surprising that some of them can also degrade plastic polymers. In this work, the biodegradation of pretreated microparticles of polystyrene and poly(vinyl chloride) was investigated using the environmentally occurring yeast Candida parapsilosis to determine the optimal conditions for the biodegradation process. MP was characterized by FTIR-ATR spectroscopy, and the number of live yeast cells (CFU) was determined during the experiment, which was then used as a response in determining the optimal biodegradation conditions. The experiments were performed according to a full factorial experimental design in which the influence of pH, optical density, and the rpm of the shaker were studied; each of these factors was investigated in three stages. In addition to the determination of CFU, TOC and HPLC/MS analyzes were also performed. Finally, the toxicity of the filtered solution after the biodegradation process was tested with the bacterium Vibrio fischeri.