Abstract: This study aimed to investigate the effects of polyculture with deposit-feeding sea cucumbers on the culture performance of Babylonia areolata and the associated aquaculture environment. Polyculture systems were established including pairwise combinations of B. areolata with Holothuria atra and H. leucospilota, a three-species polyculture system, and respective monoculture systems. A 60-day culture experiment was conducted. Variations in water nutrient concentrations were monitored, while growth performance, survival, and antioxidant and immune-related enzyme activities of the experimental organisms were measured. In addition, high-throughput sequencing was employed to analyze the microbial community structure in both water and sediment. The survival rate of B. areolata in the polyculture groups (92.00% ± 5.70%)-(97.00% ± 2.74%) was significantly higher than that in the monoculture group (56.00% ± 9.62%). Furthermore, the activities of catalase (CAT), superoxide dismutase (SOD), and lysozyme (LZM), as well as malondialdehyde (MDA) content in B. areolata, were lower in the polyculture groups than in the monoculture group. In contrast, CAT and SOD activities and MDA content in both H. atra and H. leucospilota were higher in the polyculture groups than in the monoculture groups, whereas LZM activity was lower. At the end of the experiment, the dominant bacterial phyla in both water and sediment across all treatments were Proteobacteria, Bacteroidota, Thermoplasmatota, and Actinobacteriota, with Proteobacteria being the predominant phylum. The relative abundance of Colwelliaceae in the water column showed a significant positive correlation with NH₄⁺-N concentration. Polyculture with deposit-feeding sea cucumbers effectively improves the survival rate of B. areolata and alleviates oxidative stress damage. Moreover, the mollusk-sea cucumber polyculture system enhances the self-purification capacity of the culture environment by enriching functional microorganisms involved in organic matter degradation and denitrification, thereby reducing organic loading and nitrogen accumulation in sediments and maintaining the stability of the aquaculture microenvironment. This study provides a scientific basis and practical reference for developing ecologically sustainable culture models for B. areolata.