Natural organic matter (NOM) consists of chemically heterogeneous, polyfunctional organic compounds that exist ubiquitously in aquatic and terrestrial environments. NOM forms strong complexes with metal ions and radionuclides and directly or indirectly participate in electron transfer reactions, thereby affecting chemical speciation, mobility and cycling of metals in the environment. In this presentation, coupled chemical and biological redox reactions between NOM and metal ions [e.g., iron (Fe) and mercury (Hg)] and radionuclides [e.g., uranium (U) and technetium (Tc)] are discussed. NOM is found to play multifunctional roles in mediating redox transformations of metals and radionuclides: As an electron donor under reducing conditions, NOM can rapidly reduce ferric Fe(III) to ferrous Fe(II) and transform soluble U(VI) and Tc(VII) to sparingly-soluble U(IV) and Tc(IV) solids, or mercuric Hg(II) to gaseous elemental Hg(0). As an electron shuttle, NOM also enhances the rates of biological reduction of these metals, particularly metal oxides (such as iron oxide minerals), where electron transfer or direct contact between microbes and oxide minerals may be rate-limiting. Importantly, the reduced NOM is also found to oxidize elemental Hg(0) back to Hg(II), resulting from thiol-induced oxidative complexation between Hg(II) and reduced –S in anoxic environments. In these processes, the reduced NOM converts Hg(II) to Hg(0) at relatively low NOM/Hg ratios due to the presence of reduced semiquinone moieties, but at relatively high DOM/Hg ratios, the reaction is reversed due to increased thiols and thus thiol-induced oxidation. However, as an electron acceptor under oxidizing conditions, NOM enhances the oxidation of reduced U(IV) and Tc(IV) and thus the rates of dissolution of U(IV) and Tc(IV) solids. This research highlights NOM multifunctional roles and its coupled chemical and biological reactions on redox transformations of metals and radionuclides as critical factors controlling metal speciation, transport, and geochemical cycling in the environment.