Despite the extensive application of advanced oxidation processes (AOPs) in water treatment, the efficiency of AOPs in eliminating various emerging contaminants such as halogenated antibiotics is constrained by a number of factors. Halogen moieties exhibit strong resistance to oxidative radicals, affecting the dehalogenation and detoxification efficiencies. To address these limitations of AOPs, advanced reduction processes (ARPs) have been proposed. Herein, a novel nucleophilic reductant—namely, the carbon dioxide radical anion ($\mathrm{CO}_{2}^{·-}$) —is introduced for the simultaneous degradation, dehalogenation, and detoxification of florfenicol (FF), a typical halogenated antibiotic. The results demonstrate that FF is completely eliminated by $ \mathrm{CO}_{2}^{·-}$, with approximately 100% of Cl⁻ and 46% of F⁻ released after 120 min of treatment. Simultaneous detoxification is observed, which exhibits a linear response to the release of free inorganic halogen ions (R² = 0.97, p < 0.01). The formation of halogen-free products is the primary reason for the superior detoxification performance of this method, in comparison with conventional hydroxyl-radical-based AOPs. Products identification and density functional theory (DFT) calculations reveal the underlying dehalogenation mechanism, in which the chlorine moiety of FF is more susceptible than other moieties to nucleophilic attack by $ \mathrm{CO}_{2}^{·-}$. Moreover, $ \mathrm{CO}_{2}^{·-}$- based ARPs exhibit superior dehalogenation efficiencies (> 75%) in degrading a series of halogenated antibiotics, including chloramphenicol (CAP), thiamphenicol (THA), diclofenac (DLF), triclosan (TCS), and ciprofloxacin (CIP). The system shows high tolerance to the pH of the solution and the presence of natural water constituents, and demonstrates an excellent degradation performance in actual groundwater, indicating the strong application potential of $ \mathrm{CO}_{2}^{·-}$-based ARPs in real life. Overall, this study elucidates the feasibility of $ \mathrm{CO}_{2}^{·-}$ for the simultaneous degradation, dehalogenation, and detoxification of halogenated antibiotics and provides a promising method for their regulation during water or wastewater treatment.

• $ \mathrm{CO}_{2}^{·-}$ can universally degrade and dehalogenate halogenated antibiotics;

• The chlorine moiety of FF was more susceptible to the nucleophilic attack of $ \mathrm{CO}_{2}^{·-}$;

• pH, inorganic anions and humic acid exhibited neglectable effect on FF degradation.