ABSTRACT This study investigates the effects of polyethylene glycol (PEG) on Mytilus galloprovincialis , a key sentinel species in marine environments. As PEGs are widely used in personal care products and pharmaceuticals, their increasing presence in marine ecosystems poses a potential threat to non‐target organisms. A total of 150 mussels were exposed to different concentrations of PEG (0.1 mg/L and 10 mg/L) over 14 days. The impact of PEG exposure was assessed through cell viability assays, regulatory volume decrease (RVD) tests, and histological analysis, respectively, on hemolymph and digestive gland (DG) cells, on gills, DG, and gonads. Significant reductions in cell viability were observed in hemocytes and DG cells, particularly at higher PEG concentrations. Histological analysis revealed pronounced tissue damage, including hemocyte infiltration, lipofuscin aggregation, and epithelial disorganization in the gills, hepatopancreas, and gonads, indicating PEG‐induced cytotoxicity. The study also observed impaired RVD mechanisms in DG cells, highlighting changes in cell volume regulation. These findings demonstrate that PEG can induce significant physiological and morphological alterations in marine mussels, raising concerns about its impact on aquatic ecosystems.