Entropy engineering is a flourishing topic in the field of catalyst research, but the formation of high-entropy materials is usually achieved at high temperature, which results in a trade-off relationship between entropy effect and surface area of the catalysts, thus restraining the improvements on their catalytic performance. Herein, we innovatively utilize in-situ generated polypyrrole (PPy) microspheres as the hard template, and successfully realize the preparation of porous high-entropy spinel oxides (p-HESO). The surface area of p-HESO is highly dependent on the dosage of pyrrole monomer, and the increase of surface area benefits from the restriction of PPy microspheres on the growth and aggregation of HESO particles. However, the excessive pyrrole monomer will induce phase separation. The optimal sample has a specific surface area of 65.8 m2/g and a pore volume of 0.39 cm3/g, which are 2.6 and 5.6 times of those from the conventional sol–gel method, respectively. Moreover, it is found that the utilization of PPy microspheres also promotes the generation of oxygen vacancies to some extent. The structural advantages endow p-HESO with good catalytic performance, and it can achieve the complete removal of Bisphenol A (20 ppm) within 20 min through peroxymonosulfate activation, and the corresponding reaction rate constant is about 2.25 times of conventional HESO. The potential application of p-HESO is systematically evaluated, and the influence factors include catalyst dosage, oxidant dosage, various anions, pH levels, and real water bodies. This study provides a new perspective to design porous high-entropy materials with good catalytic performance.