Radical and nonradical reaction pathways have been commonly validated in peroxymonosulfate (PMS) based advanced oxidation progresses (AOPs) using layered double hydroxides (LDHs) as catalysts, but achieving efficient and selective degradation of organic pollutants remains challenging due to the unclear regulatory mechanism of laminate M2+ in PMS activation. Here, the d-orbital electrons configuration of M2+ was found to influence the degree of overlap between M−OH and O of PMS, which results in the selective dissociation of PMS to form reactive oxygen species (ROS) or achieve electron transfer pathway. Further analysis revealed that Co(II, 3d7) and Ni(II, 3d8) with filled 3d orbital electrons can serve as electron donors for PMS, leading to the cleavage of O–O bond and the efficient generation of radical-based ROS. In contrast, Mg(II, 3d0) with unfilled 3d orbital electrons and Zn(II, 3d10) with full filled 3d orbital electrons tend to act as electron shuttles, and the outermost orbitals substantially overlap with the O of PMS to form metastable complexes. Consequently, MgAl-LDH interacts with PMS to selectively degrade quinolones as electron donor through electron transfer pathway, and its performance was not inhibited by common anions and organic matter in actual water. The above results provide a basis for optimizing the design of LDH-based catalysts according to the type of laminate M2+ to achieve high selectivity and efficiency of PMS-AOPs in water purification applications.