Organic and inorganic pollutants well known to interfere with the major functions of the endocrine system co-occur widely in contaminated ecosystems. The aim of the study was to evaluate the ability of Umbelopsis isabellina fungus to simultaneously remove and detoxify multiple environmentally significant endocrine disruptors: the heavy metals Cd(II), Zn(II), Mn(II), Pb(II) and Ni(II) and the phenolic xenobiotics nonylphenol (t-NP), 4-cumylphenol (CP) and 4-tert-octylphenol (4-t-OP). The effects of the metals on fungal growth and efficiency of single-metal uptake were also investigated. U. isabellina exhibited considerable tolerance to Zn(II), Mn(II), Pb(II) and Ni(II), with IC50/24 values ranging from 5.08 for Ni(II) to 13.1 mM for Zn(II). In the presence of CP, the maximum efficiency of Pb(II) removal increased 25% relative to that of the control. Supplementation with Mn (II) or Zn(II) enhanced the 4-t-OP degradation by 18 or 9%, respectively, after 6 h of cultivation. Ecotoxicological assays monitoring bioindicators from different aquatic ecosystems revealed detoxification coinciding with the removal of metals and organic xenobiotics from binary mixtures. This work indicates the potential of a single microorganism, U. isabellina, to remove both heavy metals and organic xenobiotics from co-contaminated sites, making it a suitable candidate for the development of bioremediation strategies.