Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). To date, there is no effective therapeutic approach for treating SARS-CoV-2 infections. MicroRNAs (miRNAs) have been recognized to target the viral genome directly or indirectly, thereby inhibiting viral replication. Several studies have demonstrated that host miRNAs target different sites in SARS-CoV-2 RNA and constrain the production of essential viral proteins. Furthermore, miRNAs have lower toxicity, are more immunogenic, and are more diverse than protein-based and even plasmid-DNA-based therapeutic agents. In this review, we emphasize the role of miRNAs in viral infection and their potential use as therapeutic agents against COVID-19 disease. The potential of novel miRNA delivery strategies, especially EDV™ nanocells, for targeting lung tissue for treatment of SARS-CoV-2 infection is also discussed.