The fate and ecological impact of antibiotics on aquatic ecosystems have not been properly elucidated in mesocosm wetlands scale. This study explored how tetracyclines (TCs, including tetracycline TC and oxytetracycline) and fluoroquinolones (QNs, including ciprofloxacin CIP and levofloxacin) affect mesocosm wetlands vegetated by V. spiralis, focusing on their impact on epiphytic biofilm microbial communities and antibiotic resistance genes (ARGs). Results showed that submerged plants absorbed more antibiotics than sediment. Both TCs and QNs disrupted microbial communities in different ways and increased eukaryotic community diversity in a concentration-dependent manner (2-4 mg/L for CIP, 4-8 mg/L for TC). TCs mainly inhibited epiphytic bacteria, while CIP increased bacterial phyla abundance. TC reduced Cyanobacteriota, Acidobacteriota, and Patescibacteria but increased Bacillota, Bacteroidota, and Armatimonadota. In contrast, CIP reduced Bacteroidota, Cyanobacteriota, and Gemmatimonadota but increased Bacillota, Planctomycetota, and Acidobacteriota. Significant differences in ARG profiles were observed between QNs and TCs, with TCs having a more substantial effect on ARGs due to their stronger impact on bacterial communities. Both antibiotics raised ARG levels with higher concentrations, particularly for multidrug resistance, tetracyclines, trimethoprim, sulfonamides, aminoglycosides, and fosfomycin, emphasizing their role in antimicrobial resistance. The study suggests that antibiotics can either stimulate or inhibit ARGs depending on their effects on bacterial communities. This study provides key evidence on the ecological mechanisms underlying the impact of TCs and QNs on epiphytic microbes of mesocosm wetlands.