Nanosized zerovalent iron (nFe0) loaded with a secondary metal such as Ni or Cu on its surface was demonstrated to effectively activate periodate (IO4−) and degrade selected organic compounds at neutral pH. The degradation was accompanied by a stoichiometric conversion of IO4 − to iodate (IO3 −). nFe0 without bimetallic loading led to similar IO4− reduction but no organic degradation, suggesting the production of reactive iodine intermediate only when IO4 − is activated by bimetallic nFe0 (e.g., nFe0 −Ni and nFe0−Cu). The organic degradation kinetics in the nFe0 −Ni(or Cu)/IO4 − system was substrate dependent: 4-chlorophenol, phenol, and bisphenol A were effectively degraded, whereas little or no degradation was observed with benzoic acid, carbamazepine, and 2,4,6-trichlorophenol. The substrate specificity, further confirmed by little kinetic inhibition with background organic matter, implies the selective nature of oxidant in the nFe0 −Ni(or Cu)/IO4 − system. The comparison with the photoactivated IO4 − system, in which iodyl radical (IO3 • ) is a predominant oxidant in the presence of methanol, suggests IO3 • also as primary oxidant in the nFe0 −Ni(or Cu)/IO4 − system.