<p>Anaerobic digestate food waste effluent (ADFE) contains high nutrient loads and causes water pollution and waste of resources if discharged without treatment. Microalgae provides a promising strategy for nutrients recovery, biomass production, and CO₂ capture. However, due to the characteristics of high ammonia nitrogen and low C/N ratio, it is hard for the original algae to remove N and P in ADFE. Hence, this study investigated the gradient domestication of <i>C. vulgaris</i> and <i>S. quadricauda</i> to enhance their tolerance to high concentrations of ADFE and evaluated their growth and metabolic responses under ADFE concentrations ranging from 20 to 60%. The results revealed that <i>S. quadricauda</i> exhibited better tolerance and growth performance compared to <i>C. vulgaris</i>, with a 42.31% biomass increase in the 40% BG11-diluted ADFE group after domestication. Additionally, extracellular polymeric substances (EPS) secretion increased by 27.66% to help shield algal cells from pollutants. The final removal efficiencies of total nitrogen, total phosphorus, and soluble chemical oxygen demand by <i>S. quadricauda</i> in BG11 dilution group were 37.13%, 40.64%, and 75.45%, respectively, which indicated that domestication alleviated oxidative stress to algal cells. This work demonstrates the simultaneous ADFE treatment and cost-effective microalgal biomass production, providing new insights into microalgal cultivation for the efficient treatment and valorization of nutrient-rich ADFE for sustainability.</p>