In the 2021 WHO classification of Tumors of the Central Nervous System, additional molecular characteristics have been included, defining the following adult-type diffuse glioma entities: Astrocytoma IDH-mutant, Oligodendroglioma IDH-mutant and 1p/19q-codeleted, and Glioblastoma IDH-wildtype. Despite advances in genetic analysis, precision oncology, and targeted therapy, malignant adult-type diffuse gliomas remain "hard-to-treat tumors", indicating an urgent need for better diagnostic and therapeutic strategies. In the last decades, miRNA analysis has been a hotspot for researching and developing diagnostic, prognostic, and predictive biomarkers for various disorders, including brain cancer. Scientific interest has recently been directed towards therapeutic applications of miRNAs, with encouraging results. Databases such as NCBI, PubMed, and Medline were searched for a selection of articles reporting the relationship between deregulated miRNAs and genetic aberrations used in the latest WHO CNS classification. The current review discussed the recommended molecular biomarkers and genetic aberrations based on the 2021 WHO classification in adult-type diffuse gliomas, along with associated deregulated miRNAs. Additionally, the study highlights miRNA-based treatment advancements in adults with gliomas. •Molecular markers enhance the WHO CNS classification, but the prognosis for adults with diffuse glioma remains poor.•miRNAs related to the genetic aberrations in adult-type diffuse gliomas might improve patient diagnostics and monitoring.•We emphasize the link between deregulated miRNAs and the genetic biomarkers used in the WHO CNS classification.•miRNA-based therapies have potential for reducing drug resistance and improving patient outcome.