The coffee industry generates substantial waste, which is often discarded, creating environmental and economic challenges. However, these residues can be a valuable source of bioactive compounds with antimicrobial properties, presenting an opportunity for their use in crop protection, both pre- and post-harvest. Following circular economy principles, this study proposes the extraction and characterization of bioactive products from coffee byproducts and evaluates their antifungal activity against pathogens affecting coffee plants and/or stored coffee beans. The proposed method for recovering coffee residues (extraction in aqueous ammonia medium followed by freeze-drying) has proven cost-effective for caffeine production and competitive with current methods. In vitro activity assays demonstrated the high antimicrobial activity of the extracts against Fusarium xylarioides, Aspergillus flavus, A. niger, and Penicillium verrucosum. The minimum inhibitory concentrations ranged from 15.6 to 375, 31.2 to 1000, 62.5 to 1000, and 62.5 to 1500 μg/mL, respectively, depending on the residue used. The extract with the highest activity, derived from silver skin, was tested for the pre-harvest protection of coffee plants and the post-harvest protection of coffee beans. At a concentration of 62.5 μg/mL, it demonstrated complete control of tracheomycosis caused by F. xylarioides in coffee plants and full protection of coffee beans against A. flavus, A. niger, and P. verrucosum. These findings suggest that aqueous ammonia extracts of coffee byproducts represent a promising alternative to conventional synthetic phytosanitary products, with the potential to improve the sustainability of the coffee industry.