<p>The mesoporous carbon-loaded nickel cobaltate nanoparticles (nano-NiCo₂O₄@MC) with several active sites were successfully prepared by using a hydrothermal approach for the degradation of tetracycline (TC) by activated peroxymonosulfate (PMS). Under optimal conditions, the nano-NiCo₂O₄@MC/PMS system exhibited remarkable catalytic efficiency, achieving a TC degradation rate of 99.5% in 5 min, and the first-order reaction rate constant is 4.42 times that in the nano-NiCo₂O₄/PMS system. Electron paramagnetic resonance tests and quenching experiments indicate that ¹O₂, O₂^·−, and SO₄^·− play a crucial role in the degradation of TC. Furthermore, electron mobility was enhanced and free radical production was encouraged by the redox cycling of Co²⁺/Co³⁺ and Ni³⁺/Ni²⁺ on the catalyst surface. Significantly, the extensive specific surface area and pore volume in the catalyst, due to the incorporation of mesoporous carbon, facilitated the ionic valence exchange among different metal ions. TC is converted into multiple intermediates via two distinct pathways and ultimately forms inorganic small molecules. Toxicity analysis revealed a reduction in the intermediate toxicity following the catalytic reaction. Furthermore, the nano-NiCo₂O₄@MC/PMS system demonstrated remarkable stability, recyclability, anti-interference ability, and universality. This study provides a novel design strategy of heterogeneous catalytic material and finds an effective method to remove TC from the water environment.</p>