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MicroRNAs ( miRNAs) are highly conserved, 19-23 nucleotide long, non-coding, endogenous RNA, which are transcribed from either intergenic, intronic or polycistronic regions and modulate gene expression through mRNA degradation or translational repression. They are fine tuners of biological processes and have recently emerged as biomarkers and therapeutic targets of cardiovascular diseases. Several miRNAs regulate stem cell for differentiation, proliferation and degeneration. Stem cells are pluripotent, self-renewing and clonogenic cells having tremendous potential for regenerative therapy. The current therapeutic approach is unable to cope up with rapidly increasing rates of diabetes and cardiovascular diseases. The empirical and clinical evidences revealed that transplantation of exogenous stem cells can regenerate beta cells in diabetic patients and myocardium in patients with myocardial infarction. Nevertheless, the major limitation of stem cell therapy is unpredictable behavior of exogenous stem cells that incur few reports of teratoma and cancer after transplantation. Therefore, understanding the regulation of newly transplanted stem cells into the foreign body is a major challenge to translational research / clinical trail. Since miRNA plays pivotal role in the fine regulation of proliferation and differentiation of stem cells, investigations on the regulation of miRNA in transplanted stem cells in a specific micro-environment that houses the stem cell is indispensable. Additionally, the inhibition or over expression of specific miRNAs in the niche surrounding the stem cell will be crucial for maintaining the specific lineage of exogenous stem cells. This review embodies major advancement in the field of miRNA biogenesis and its regulatory mechanisms, role of different miRNAs and stem cells as a therapeutic target for diabetes and cardiovascular diseases. It also provides insights into the novel future therapy, where synergistic approach for manipulating miRNAs and stem cells will emerged as a potential treatment for diabetes and cardiovascular diseases.