Pleurotus ostreatus (Jacq. ex Fr.) P. Kumm mushrooms are cultivated on diverse by-products based on substrates that hold promise for mitigating antibiotic usage in the poultry industry and reducing environmental pollution. By incorporating agricultural by-products into mushroom cultivation, the functionality of the mushroom products can be increased, then the final product can be a more effective feed supplement. After mushroom cultivation, spent mushroom substrate (SMS) can be valorized, due to the presence of huge amounts of bioactive compounds like β-glucan, chitin, polyphenols, and flavonoids related to mycelia. As a prebiotic and antimicrobial feed supplement, these mushrooms positively influence gut microbiota, intestinal morphology, and thus overall poultry well-being. This article underscores the potential of solid-state fermentation (SSF) to enhance the bioactivity of oyster mushrooms and their derivatives, offering a cost-effective and efficient strategy for transforming unconventional feeding materials. Moreover, it emphasizes broader implications, including the reduction of antibiotic dependence in poultry farming, highlighting the promising integration of oyster mushrooms and their derivatives for sustainable and environmentally conscious poultry production.