Nonpathogenic microorganisms are known to be part of the normal gut microflora of animals and specifically play vital roles in fish physiology. They have wide-ranging bioactive molecules with high potential to fish’s general health. However, in some instances, it has been reported that irregular gut microbial interactions, pH, and nutrient fluctuations limit the potential activities and benefits of gut microflora. Therefore, as an alternative, the bioactive molecules of this nonpathogenic organism are biotechnologically harnessed and processed for use as additives in fish feeds, by identifying, mass culturing, extracting their extracellular metabolites, and processing them into storable forms for subsequent use. The biotechnology of producing extracellular metabolites from living things, in particular, microorganisms, is now feasible from previously identified and characterized nonpathogenic isolates. Biotechnological applications use biological systems, living organisms, or derivatives thereof, to make or modify products or processes for specific purposes essentially targeted at benefitting humans as end users. Research has shown that optimization of microbial growth and extraction of their metabolites for therapeutic and nutritional purposes are now gaining more relevance and adding high value to aquaculture production, concerning aquaculture nutritional biotechniques. They can secrete a full complement of secondary metabolic products which are known to be effective therapeutics such as antibiotics, growth promoters such as amino acids, and other biomolecules like enzymes that catalyze metabolism. This chapter therefore focuses on the sources, types, and uses of metabolites. The nutrient requirements of microbial growth, biotechnological, and bioeconomic relevance will also be discussed for sustainable activities in the Global South.