Radiolabeling counts for much in the functionalization of inorganic nanoparticles (NPs) because it endows NPs with high‐sensitive imaging capacities apart from providing accurate pharmacokinetic information on the labeled particles, which makes the development of relevant radiolabeling chemistry highly desirable. Herein, a novel Ligand Anchoring Group MEdiated RAdioLabeling (LAGMERAL) method is reported, in which a polyethylene glycol (PEG) ligand with a diphosphonate (DP) terminal group plays a key role. It offers possibilities to radiolabel NPs through the spare coordination sites of the DP anchoring group. Through X‐ray absorption spectroscopy studies, the coordination states of the foreign metal ions on the particle surface are investigated. In addition, radioactive Fe3O4 NPs are prepared by colabeling the particles with 125I at the outskirt of the particles through a phenolic hydroxyl moiety of the PEG ligand, and 99mTc at the root of the ligand, respectively. In this way, the stabilities of these types of radiolabeling are compared both in vitro and in vivo to show the advantages of the LAGMERAL method. The outstanding stability of probe and simplicity of the labeling process make the current approach universal for creating advanced NPs with different combinations of functionalities of the inorganic NPs and radioactive properties of the metal radioisotopes.