In our continued search for biologically active metabolites from cultures of rare Basidiomycota species, we identified twenty-two previously undescribed compounds from submerged and solid-state cultures of three European Basidiomycetes belonging to family Hericiaceae namely: Dentipellis fragilis, Hericium flagellum and H. coralloides (1–4). Their chemical structures were unambiguously determined based on extensive 1D and 2D NMR spectroscopy along with HR-ESI-MS analyses. The isolated compounds revealed different biological effects. Some exhibited significant activities in our standardized cell-based assays for the determination of cytotoxic and antimicrobial effects. In addition, most of the compounds demonstrated neurotrophic effects. These were determined using the rat pheochromocytoma cell (PC-12)-based assay for neurite outgrowth promotion and real-time quantitative reverse transcription polymerase chain reaction (RT-qPCR) assay, to assess the effects of the compounds on the expression of neurotrophins NGF and brain-derived neurotrophic factor (BDNF) on human astrocytoma cells.