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Tilapia culture is one of the largest sectors of global aquaculture. Among the different species of tilapia, Nile tilapia (Oreochromis niloticus) is perhaps the top cultured species. The production of Nile tilapia has been continually increasing throughout the years resulting in genetic deterioration. Several tilapia strains with better growth performance and adaptive capability to survive in different culture conditions have been developed to alleviate the crisis. Increased demand for Nile tilapia implies higher farming cost. Plant-based proteins are utilized as partial or complete fishmeal replacements to reduce feed cost. However, these proteins can adversely affect and alter growth and feed performance, carcass composition and indices, and gut and hepatic health. This review discusses the use of seven plant-based proteins: namely, soybean, copra, pea, corn, palm kernel, microalgae, and seaweed as a Nile tilapia aquafeed. Different processing methods are employed to produce several types of plant-based proteins. Processed plant-protein types, when utilized as an aquafeed ingredient, vary in its effect on the performance, hemato-immunological parameters, and gut and hepatic health of Nile tilapia. Studies have shown that Nile tilapia can effectively maximize plant-based protein diets based on the preparation method, type of plant source, amino acid supplementation, and inclusion levels of the plant proteins. These readily available crops should be considered as primary protein sources for aquaculture. Hindrances to the use of plant-based proteins as a main dietary protein are limiting amino acids, presence of anti-nutritional factors, and the competition between its demand as human food and as animal feed.