The　presence　of　antibiotics　in　wastewater　threatens　the　human　living　environment.　Activated　peroxymonosulfate　(PMS)　method　is　often　used　for　catalytic　degradation　of　antibiotics.　However,　how　to　reduce　catalyst　cost　and　ensure　efficient　degradation　of　antibiotics　at　the　same　time　is　a　sticky　issue　for　the　activated　PMS　method.　Two-dimensional　vermiculite　flakes　(2D-VMT)　is　cost-effective　and　can　be　used　as　catalyst　carriers　for　PMS　activation.　Hence,　we　exfoliated　2D-VMT　from　natural　vermiculite　and　prepared　NiCo2O4　loaded　2D-VMT　(NiCo2O4/2D-VMT)　catalyst.　Levofloxacin　(LVX),　as　a　normal　antibiotic,　was　used　to　evaluate　the　catalytic　capacity　of　NiCo2O4/2D-VMT　in　PMS　systems.　Also,　LVX　degradation　mechanism　through　NiCo2O4/2D-VMT　activated　PMS　were　explored　here.　XRD,　EDS,　TEM,　and　HRTEM　analysis　all　demonstrated　NiCo2O4　nanoparticles　were　successfully　anchored　on　2D-VMT.　NiCo2O4/2D-VMT　had　a　high　specific　surface　area　and　abundant　active　sites.　The　NiCo2O4/2D-VMT/PMS　system,　with　a　15%　mass　ratio　of　NiCo2O4　to　2D-VMT　(15%-CN/2D-VMT),　achieved　LVX　removal　efficiency　of　87%　and　LVX　removal　rate　of　0.034　min−1.　1O2　and　SO4·-　were　the　major　ROS　for　LVX　degradation.　The　reversible　redox　cycle　between　Co(III)/Co(II)　and　Ni(III)/Ni(II)　played　a　crucial　role　in　activating　PMS　to　generate　ROS　for　LVX　degradation　process.　Also,　based　on　intermediates　identification　by　LC-MS,　possible　degradation　pathways　of　LVX　were　proposed　and　their　ecotoxicological　evolution　was　assessed　by　using　the　ECOSAR　software.　15%-CN/2D-VMT　may　be　a　worth　recommended　loaded　catalyst　for　antibiotics　removal　in　environmental　remediation,　owing　to　its　high　reusability　and　excellent　renewability.　©　2024　Elsevier　Ltd