In this work, a novel method for the preparation of high-entropy oxides (HEO) was successfully developed using multivariate composition layered double hydroxides (LDHs) as precursor. Thermal treatment over 600 °C led to the complete transformation of LDHs to single spinel phase HEOs. The performance of the obtained HEO catalysts in the removal of volatile organic compounds (VOCs) was studied with the catalytic oxidation of toluene as the probe reaction. The optimized HEO-600 catalyst showed impressive activity and stability over toluene catalytic oxidation, which resulted from the vast quantity of surface oxygen vacancies and the relative variable metal valence. The T₅₀ and T₉₀ values of HEO-600 were 246 and 254 °C, and the T₉₀ value only presented a slight increase to 265 °C after a 10-cycle test. This work developed a simple way to obtain HEO materials and provide technical support for the application of HEO catalysts for VOCs removal.