The increasing demand for sustainable aquafeed ingredients has driven the exploration of alternative protein sources to replace conventional fishmeal and soybean meal. Defatted algae cake (DAC), a by-product of microalgae-based biofuel production, presents a promising and eco-friendly protein source for aquaculture. This review examines the potential of DAC as a sustainable alternative feed ingredient by assessing its nutritional composition, inclusion levels, digestibility, economic feasibility, and environmental benefits. Rich in proteins, essential amino acids, bioactive compounds, and functional lipids, DAC has demonstrated positive effects on fish growth, feed efficiency, and immune responses when incorporated at optimal levels. However, high production cost, variability in nutrient composition, the presence of anti-nutritional factors, and species-specific dietary requirements pose challenges to its widespread application. Comparative analyses indicate that DAC inclusion levels at optimal levels, generally under 10% in fish feed, can maintain growth performance across various species, while higher levels may impact digestibility, feed efficiency, and nutrient bioavailability. The economic viability of DAC is influenced by its cost relative to traditional feed ingredients, advancements in processing, improved digestibility for fish, and integration within circular bioeconomy models. Additionally, its use in aquaculture contributes to sustainability by reducing reliance on overexploited marine resources and mitigating environmental impacts associated with fishmeal and soybean meal production. This review highlights the need for further optimization in DAC processing and formulation to enhance its utilization as a cost-effective and sustainable aquafeed ingredient, supporting the long-term growth of the aquaculture industry.