Various transition metals (Fe, Mn, Cu and Ni) were doped into ordered mesoporous Co₃O₄ to synthesize Co₃O₄-composite spinels. Their formation was evidenced by transmission electronic microscopy (TEM), X-ray diffraction (XRD) and Brunauer–Emmett–Teller (BET) analysis. It was found that Co₃O₄-composite spinels could efficiently activate peroxymonosulfate (PMS) to remove enrofloxacin (ENR) and the catalytic activity followed the order Co₃O₄–CuCo₂O₄ > Co₃O₄–CoMn₂O₄ > Co₃O₄–CoFe₂O₄ > Co₃O₄–NiCo₂O₄. Moreover, through the calculation of the specific apparent rate constant (k_sapp), it can be proved that the Co and Cu ions had the best synergistic effect for PMS activation. The Co₃O₄-composite spinels presented a wide pH range for the activation of PMS, but strong acidic and alkaline conditions were detrimental to ENR removal. Higher reaction temperature could promote the PMS activation process. Sulfate radical was identified as the dominating reactive species in Co₃O₄-composite spinel/PMS systems through radical quenching experiments. Meanwhile, the probable mechanisms concerning Co₃O₄-composite spinel activated PMS were proposed.