Microalgal-bacterial system has been considered as one of the most promising methods for treating wastewater, while it is hampered by the loose structure of suspended sludge, leading to low removal efficiency and system stability for multiple pollutants in aquaculture wastewater treatment. This study firstly explored the crucial conditions for microalgal-bacterial granular sludge (MBGS) formation, i.e., bacterial-microalgal ratio (BMR) and light intensity, and application for aquaculture wastewater treatment. The formation of MBGS was characterized and depicted from multiple perspectives, e.g., MLSS, MLVSS, EPS content, particle sizes, and hydrophobicity, all these results demonstrated that optimal conditions for MBGS were BMR of 5 and light intensity of 1800 lx. The MBGS showed excellent removal performance for aquaculture wastewater contained salinity (- 0.3 %), the removal efficiencies of COD (- 1000 mg/L), NH4+-N (- 100 mg/L), and PO43--P (- 10 mg/L) reached 90.2 f 5.8 %, 77.1 f 9.5 %, and 54.8 f 6.0 %, respectively. Meanwhile, approximately 60 % of enrofloxacin (i.e., ENR, 100 mu g/L) was also stable removed under the stress of salinity. The microbial community and co-occurrence network analysis showed that nitrite-oxidizing bacteria (e.g., Nitrosomonas), denitrifying bacteria (e.g., Thauera and Comamonas), and polyphosphate accumulating bacteria (e.g., Acinetobacter) and microalgae (e.g., Trebouxiophyceae and Chlorophyceae) were the main microorganisms, and their cooperative interaction contributed to the MBGS formation and excellent C, N, P, and ENR removal. This study depicted detailed the MBGS formation and provided a novel perspective on advantage and potential of the optimized microalgal-bacterial sludge granulation in aquaculture wastewater treatment within salinity and antibiotic contamination.