Conventional biological treatment processes cannot efficiently and completely degrade nitroimidazole antibiotics, due to the formation of highly antibacterial and carcinogenic nitroreduction by-products. This study investigated the removal of a typical nitroimidazole antibiotic (ornidazole) during wastewater treatment by a biological sulfidogenic process based on elemental sulfur (S⁰-BSP). Efficient and stable ornidazole degradation and organic carbon mineralization were simultaneously achieved by the S⁰-BSP in a 798-day bench-scale trial. Over 99.8 % of ornidazole (200‒500 μg/L) was removed with the removal rates of up to 0.59 g/(m³·d). Meanwhile, the efficiencies of organic carbon mineralization and sulfide production were hardly impacted by the dosed ornidazole, and their rates were maintained at 0.15 kg C/(m³·d) and 0.49 kg S/(m³·d), respectively. The genera associated with ornidazole degradation were identified (e.g., Sedimentibacter, Trichococcus, and Longilinea), and their abundances increased significantly. Microbial degradation of ornidazole proceeded by several functional genes, such as dehalogenases, cysteine synthase, and dioxygenases, mainly through dechlorination, denitration, N-heterocyclic ring cleavage, and oxidation. More importantly, the nucleophilic substitution of nitro group mediated by in-situ formed reducing sulfur species (e.g., sulfide, polysulfides, and cysteine hydropolysulfides), instead of nitroreduction, enhanced the complete ornidazole degradation and minimized the formation of carcinogenic and antibacterial nitroreduction by-products. The findings suggest that S⁰-BSP can be a promising approach to treat wastewater containing multiple contaminants, such as emerging organic pollutants, organic carbon, nitrate, and heavy metals.