<p>The miRNA-based therapeutics held great promise for the treatment of diseases associated with aberrant gene expression. However, the development of miRNA-based drugs still faces many obstacles, including stability, targetability, tissue penetration, and induction of immune responses. To overcome these challenges, researchers developed various miRNA modification methods and miRNA-based delivery systems, which can protect miRNA from degradation and facilitate their transport across biological barriers. Here, we give an overview of the latest advancements in a variety of delivery systems, including virus, lipid, polymer, inorganic, and exosome-based nanosystems, which have been proved as versatile and valuable carriers for miRNA. Moreover, the use of stimuli-responsive materials allows for the controlled release of oligonucleotides in response to specific triggers. Importantly, the current miRNA-based therapeutics in clinical trials are summarized in this review. The combination of these advancements has the potential to promote more effective and safer treatment designs for a wide range of diseases. This review will contribute to developing more precise targeted delivery systems of miRNA, ultimately facilitating its clinical development.</p> Graphical Abstract <p></p>