Previous studies have shown that O3/Peroxymonosulfate (PMS) outperforms O3 alone in treating refractory pharmaceuticals and personal care products. However, research on the removal of antibiotics using O3/PMS remains limited, and the effectiveness of this process in removing antibiotic-resistant bacteria (ARB) and antibiotic resistance genes (ARGs) remains unclear. In this study, the treatment performance of O3 and O3/PMS for antibiotic-containing wastewater were comprehensively compared, particularly on the effectiveness of O3/PMS in inactivating ARB and reducing ARGs abundance compared with O3. Within 15 min of treatment, O3/PMS removed up to 52.3 % more targeted antibiotics, 4.8 % more dissolved organic carbon, 2.7 % more UV254, and 18.8 % more dissolved organic matter (DOM) than O3. For ciprofloxacin-resistant and chloramphenicol-resistant bacteria, both O3 and O3/PMS showed a continuous decrease in concentration with increasing treatment time. For amoxicillin-resistant, tetracycline-resistant, and sulfamethoxazole-resistant bacteria, O3 showed an initial increase followed by a subsequent decrease, while O3/PMS showed a similar trend for tetracycline- and sulfamethoxazole- resistant bacteria, but a continuous decrease for amoxicillin-resistant bacteria. For ARGs, before 8 min, O3 treatment showed a higher relative abundance of targeted ARGs (0.01-0.31 ARGs/16S rRNA), mainly due to tetQ. After 8 min, O3/PMS treatment exhibited a higher relative abundance of ARGs/16S rRNA (0.04-0.05), primarily due to floR. At the phylum level, PMS addition increased Bacteroidota abundance while reducing Proteobacteria, Chloroflexota, and Myxococcota_A_473307. At the class level, PMS specifically promoted Alphaproteobacteria and Bacteroidia while inhibiting Gammaproteobacteria and UBA9160. Finally, the acute toxicity of O3/PMS-treated wastewater was 14.6 % lower than that of O3-treated wastewater at 2 min. However, after 6 min, the toxicity of O3/PMS-treated wastewater became significantly higher, with the largest difference (23.6 %) observed at 8 min. The results indicated that O3/PMS had an advantage over O3 in removing antibiotics, DOM, and controlling ARB. However, prolonged treatment increased ARGs diversity and concentration compared to O3 and significantly enhanced the acute toxicity of antibiotic-containing wastewater.