Wastewater treatment plants are essential infrastructures for protecting aquatic ecosystems, as they remove chemical and biological contaminants from domestic, industrial, and agricultural effluents before environmental discharge. Wastewater commonly contains fine suspended and dissolved solids, including inorganic and organic particles, whose small size makes their removal particularly challenging. Among available technologies, coagulation and flocculation are widely applied for colloid removal and rely on polymeric compounds of either synthetic or natural origin. Although only a limited fraction of these compounds is expected to remain in the treated effluent, their extensive use raises concerns regarding potential impacts on aquatic ecosystems.To evaluate the ecotoxicological effects of selected flocculants and coagulants, Daphnia magna was used as a model organism. Due to the limited information available on the environmental occurrence, fate, and toxicity of these polymers, a preliminary range-finding test was performed. Based on the 48-h immobilization assay, EC10 concentrations were selected and applied in a 14-day chronic exposure experiment under environmentally relevant conditions. The tested compounds were selected from a previous study identifying the most effective treatments for the removal of organic matter and plastic particles from wastewater. Polyacrylamides, starch-based, and tannin-based compounds were evaluated as flocculants, while poly-aluminum chloride was tested as a coagulant. Effects were assessed from organismal to cellular levels, including immobilization, growth, behavior, reproduction, feeding activity, oxidative stress, neurotoxicity, and energy metabolism biomarkers. Preliminary results suggest markedly higher toxicity associated with synthetic flocculants, with immobilization rates ranging from 90% to 100%. In contrast, naturally derived compounds exhibited lower toxicity while maintaining high removal efficiency for both chemical contaminants and plastic particles, highlighting their potential as more sustainable alternatives for wastewater treatment applications.