ZnO nanoparticles (ZnO NPs) are widely used in medicine, food preservation, and other industres. The current study aims to evaluate the toxic effect of zinc oxide-agar nanocomposites on Coelatura aegyptiaca which is considered as a sensitive bioindicator for environmental pollution. Following the synthesis and characterization of zinc oxide nanoparticles (ZnO NPs) and ZnO-agar, different doses (12.5, 25, 50 mg/L) were tested. In addition to histology investigation, oxidative stress indicators were examined after seven days. ZnO NPs and ZnO-agar nanocomposite (NC) caused a significant increase in malonaldehyde and nitric oxide concentrations, while they decreased glutathione and catalase levels. Furthermore, bivalves treated with ZnO NPs and ZnO-agar NC showed structural alterations in their gills and mantle. In general, using agar in the synthesis of ZnO NPs results in synergistic effects such as cellular and structural damage and a more prominent alteration in biochemical parameters. In addition, we found that Coelatura aegyptiaca is an effective bioindicator for nanoparticle toxicity and water pollution.