Tetracycline (TC) stress disrupts microbial communities, yet its impact on aerobic granular sludge (AGS) formation and stability remain poorly understood. This study employs quantitative proteomics to unravel the AGS adaptive mechanisms under continuous TC exposure (1 mg/L). The results demonstrated that TC accelerated AGS granulation, achieving stable structure within 20 days, accompanied by improved pollutants removal and settling performance. A critical granule size threshold of 3-4 mm was identified, beyond which AGS exhibited destabilization tendencies. Extracellular polymeric substances (EPS), particularly proteins, play pivotal role in maintaining AGS stability, with the α-helix / (β-sheet + irregular curl) ratio correlated with granule integrity. Proteomic analysis revealed the upregulation of outer membrane protein A (OmpA), facilitating biofilm formation, while TC-targeted ribosomes and bacterial chemotaxis were identified as central mechanisms for TC resistance and stress adaptation, respectively. These findings uncover molecular adaptations driving AGS stability under antibiotic pressure and offer insights for optimizing high-antibiotic wastewater treatment.