ABSTRACT This paper aimed to apply filamentous fungi (Penicillium oxalicum and Cunninghamella echinulata), the microalga Tetradesmus obliquus and their co-culture in advanced treatment (tertiary treatment) of cheese whey. The bioremediation process was carried out in agitated flasks and bubble column bioreactors with different concentrations of chemical oxygen demand (COD) (223–1663 mg L − 1), total nitrogen (TN) (13–61 mg L − 1), and total phosphorus (TP) (3–26 mg L − 1). The results obtained in shaken flasks showed a superiority of the consortium compared to the systems with separated species. In this sense, the treatment was carried out in a bubble column reactor, and the consortium formed by the microalga and the fungus C. echinulata showed a greater efficiency (at a light intensity of 100 µmol m − 2 s − 1), promoting by the symbiosis to reach removal efficiencies of up to 93.7, 78.8 and 93.4% for COD, TN and TP, respectively; meeting Brazilian and European standards for discharge into water bodies. In addition, no pH adjustment was required during the co-culture treatment, demonstrating the buffering effect of using these two types of microorganisms. Therefore, the use of the consortium formed by T. obliquus and C. echinulata as a remediator was highly promising to promote the advanced treatment of cheese whey.