Layered double hydroxides (LDHs) are a class of layered materials with tunable interlayer galleries. In this paper, a series of Mg3Al–P2W17X (X = MnIII, FeIII, ZnII, CoII, CuII, NiII) have been prepared successfully by intercalating the polyoxometalate (POM) of [α2-P2W17O61(X·OH2)]n− ([P2W17X]n−, n = 7 or 8) into a Mg3Al–suberic precursor. Catalytic tests for H2O2-based sulfoxidation of various sulfides demonstrate that Mg3Al–P2W17Zn exhibits better catalytic efficiency and selectivity than pure POM or LDH precursors under mild conditions. The uniform and well-ordered dispersion of POM in the confined gallery of LDHs and the multiple interactions between POMs and LDHs contribute to the excellent catalytic performance. Moreover, Mg3Al–P2W17Zn is stable and can be easily separated from the reaction system. The recycled Mg3Al–P2W17Zn maintains both the intact structures of the POM anion and LDHs. The scaled-up experiment provides further support for its potential use for industrial applications.