Food by-products have gained interest in recent years due to the necessity of reprocessing food waste as food demand continues to increase worldwide, affecting the environment and society’s health. Nowadays, food by-products are used mainly for animal feed, composting, and bioenergy production. However, sustainable strategies have been elucidated to obtain eco-friendly products through innovative organic waste management, including emerging technologies such as ultrasound and microwave to modify by-product structures or extract high-value molecules, and with microbial-based technologies where conventional and non-conventional microorganisms have been isolated from different environments and cultivated in solid and liquid state systems. Bioprospection of bacteria, yeast, and fungi through these systems has shown remarkable results in obtaining enzymes, pigments, flavors, and bioactive compounds, among other natural bioproducts, from non-expensive and abundant substrates derived from food by-products. These bioproducts have been produced mainly from fruit, vegetables, and lignocellulosic by-products.