<p>Cancer stem cells (CSCs), refer to small subpopulations of cancer cells within a tumor mass representing stemness properties such as high self-renewal capacities, differentiation potential, metastasis, therapy resistance, and tumor recurrence. These cells are the main reason for cancer treatment failure and the inefficacy of traditional therapeutic approaches. Accordingly, focusing on molecular mechanisms underlying CSCs and targeting them is the new era in the field of cancer. MicroRNAs (miRNAs) are a class of noncoding RNAs that play an important role in the formation and progression of CSCs by regulating the expression of stemness markers and critical genes implicated in CSC signaling pathways. Many studies have reported that some miRNAs have aberrant expression in CSCs. Dysregulated miRNAs can be a promising candidate as a therapeutic target for eradicating CSCs, but their delivery into CSCs could be challenging. Notably, numerous studies have shown that natural nanoparticles such as exosomes and chitosan nanoparticles (CSNPs) are among the most extensively exploited nano vehicles for miRNA delivery. In the present review, we focus specifically on CSNPs- and exosome-based CSC-targeted therapies and provide the key advantages and shortcomings of these systems as miRNA delivery systems for targeting CSCs.</p>