Ionizing radiation has attracted significant interests in water purifying. However, it suffers from poor mineralization performance during the decontamination of organic micropollutants such as antibiotics. Herein, the radiolytic degradation of sulfathiazole (STZ) by gamma radiation was investigated. STZ could be completely degraded at 2.0 kGy absorbed dose but TOC removal efficiency was only 22.62 %. Quenching experiments demonstrated that •OH was the main reactive species. Toxicity assessment and phytotoxicity experiments indicated that gamma radiation can comprehensively decrease the toxicity of STZ. Significant enhancements of degradation and mineralization were observed in gamma/persulfate (Gamma/PS) and gamma/periodate (Gamma/PI) processes. The rate constant (k) increased by 1.08 times and TOC removal efficiency increased by 2.01 times with PS addition (1 mM). The k value enhanced by 4.05 times and TOC removal ratio enhanced by 2.66 times with the presence of PI (1 mM). Mechanistic investigation indicated that 1O2 played a major role in STZ degradation in the Gamma/PS and Gamma/PI systems. PI was almost completely transferred into the nontoxic iodate (IO3-), and no toxic reactive iodine species were produced in the Gamma/PI process. Moreover, Gamma/PS and Gamma/PI systems showed a broad-spectrum ability to remove a series of antibiotics. The removal performances and the costs of these systems were competitive compared with other advanced oxidation processes for antibiotics elimination. This study supplied an efficient and sustainable choice for the degradation of antibiotics, and clarified the intrinsic reaction mechanisms in the ionizing radiation-activated PS and PI systems.