Certain mushrooms, especially basidiomycetes, may offer an eco-friendly alternative to synthetic pesticides. This chapter outlines how mushroom-derived compounds can fight off crop diseases through natural mechanisms like antibiosis, competition, and induced resistance. These fungi produce secondary metabolites with antiviral, antifungal, and antibacterial effects, and some can even target plant-parasitic nematodes. By harnessing these properties, mushrooms could help farmers manage pests and diseases while reducing chemical use and environmental harm.