Biopesticides are organisms, products or byproducts of plants, animals, microorganisms and insects that are used to control pests and diseases in plants and animals. Macrofungi are higher fungi belonging to the phyla Basidiomycota and Ascomycota that are highly adaptable to diverse environments and have a unique and remarkable capacity to synthesise secondary metabolites with diverse properties, modes of action and functions. Hence, they constitute important sources of biopesticides, serving as safe and environment-friendly alternatives to synthetic pesticides that are currently eschewed due to toxicity and gaining increased acceptance for controlling agricultural pests and diseases. Macrofungal species are highly suitable for extraction of metabolites because they are widely available and easily cultivable. The development of these natural compounds is achievable in scale-up systems utilising natural or recalcitrant substrates (lignocellulosic solid wastes) for production. However, challenges exist for metabolite formulation, registration and commercialisation. The bioactive potential of the mycelial metabolites of various species of macrofungi with biopesticidal activities against plant pathogenic bacteria, fungi, nematodes and bioherbicidal activities are discussed in this chapter.