Environmental contamination with microplastics and trace pharmaceuticals is an increasing ecological and health concern. This study aimed to investigate the effects of low-temperature cold plasma on polyethylene (PE) microplastic particles and to assess the potential for degradation of pharmaceuticals adsorbed onto their surfaces. Two types of PE samples were prepared: suspended in distilled water and in treated wastewater. All samples were exposed to cold plasma. In the second stage, PE particles were saturated with selected pharmaceuticals (diclofenac, sulfamethoxazole, trimethoprim) and then subjected to plasma treatment. Pharmaceutical concentrations were measured using high-performance liquid chromatography (HPLC). Particle morphology was analyzed via light microscopy (after Nile red staining) and scanning electron microscopy (SEM). The results showed that cold plasma treatment leads to agglomeration of PE particles, with the extent increasing with longer plasma exposure time. Pharmaceuticals adsorbed to the PE surface in the range of 20–70% of the applied dose. Cold plasma demonstrated the ability to remove pharmaceutical contaminants, particularly diclofenac (>98%), sulfamethoxazole (99.99%) and trimethoprim (>98%). These findings indicate that cold plasma has promising potential as a supportive technology for removing both microplastics and pharmaceutical residues from wastewater and aquatic environments.