Growing mushrooms means meeting challenges while aiming for sustainability and circularity. Wherever the producer is located, commercial strains are the same originating from several producers. Customized strains adapted to local conditions are urgently needed. Before introducing new species to the strain development pipeline, the chemical characterization and biological activity of wild ones need to be assessed. Accordingly, the mycoceutical potential of five polypore mushroom species from Serbia was evaluated including: secondary metabolite composition, oxidative damage prevention, anti-tyrosinase, and anti-angiotensin converting enzyme (ACE). The phenolic pattern was comparable in all samples, but the amounts of specific chemicals varied. Hydroxybenzoic acids were the primary components. All samples had varying quantities of ascorbic acid, carotene, and lycopene, and showed a pronounced inhibition of lipid peroxidation (LPx) and ability to scavenge HO•. Extracts were more potent tyrosinase inhibitors but unsuccessful when faced with ACE. Fomitopsis pinicola had the strongest anti-tumor efficacy while Ganoderma lucidum demonstrated strong selectivity in anti-tumor effect in comparison to normal cells. The evaluated species provided a solid foundation for commercial development while keeping local ecology in mind.