It has been proposed that marine mucilage intensifies the biological effects of chemical pollutants and can increase their bioaccumulation in seafood. Indeed, in 2021, mucilage caused a major environmental disaster in the Sea of Marmara. Limited resources on the possible effects of marine mucilage on sustainable food security have increased the importance of this study. The aim of this study is to investigate the biochemical effects of mucilage in wild and cultured mussels, a bioindicator species collected from four different regions [Istanbul Strait (S1) and Canakkale Strait (S2), Bandirma (S3), Gelibolu (S4)] during the 2021 fishing season in the Sea of Marmara. The levels of reduced glutathione and lipid peroxidation, activities of antioxidant enzymes like glutathione reductase, glutathione-S-transferase, catalase, superoxide dismutase, activities of biomarker enzymes like alanine aminotransferase, aspartate aminotransferase, and lactate dehydrogenase activities were determined. Our findings demonstrated that mucilage had an impact on cellular oxidative state and compromised the lipid cell membranes in the mantle tissues of Mediterranean mussels (Mytilus galloprovincialis, Lamarck 1819). It was found that there is a high positive relationship between seawater temperatures and bioparameters in S2 and S3 regions, except for GSH level. This study puts forward that in the presence of marine mucilage the biological responses and the state of health of mussels are negatively affected. Parameters which exhibit this kind of response may be used as biomarkers of exposure to marine mucilage in wild and culture mussel populations. Environmental disasters such as marine mucilage naturally affect food security by putting the sustainability of these species at risk.