Poor catalytic activity and stability are primary defects of traditional Pd/Al2O3 catalysts for the low-temperature methane combustion. Herein, we developed a facile way to synthesize a MgAl-LDHs derived MgAl2O4 spinel with good crystalline lattice and high surface area, which was used as support of Pd-based catalysts. Catalysts with Mg/Al ratio of 1/3 presented the highest methane combustion activity. It was found the well-crystallized MgAl2O4 spinel promoted the dispersion and crystallization of PdO due to the strong interaction between PdO and support, and the electrophilicity and basicity originated from Mg doping suppressed the sintering of PdO particles, leading to the excellent performance of Pd/MgAl3. Moreover, these factors also inhibited the formation of surface OH- species, therefore, improved the water resistance. Such a synthesis strategy of the Pd/MgxAly derived from LDHs and the roles of MgAl2O4 spinel could pose some meaningful directions for developing high-efficient Pd-based catalysts for the low-temperature methane combustion.