miRNAs are small, non-coding RNAs, functioning as negative suppressors of target gene expression. A significant proportion of the transcriptome is subject to miRNA modulation. A single miRNA determines the expression of hundreds of genes, while miRNAs are relatively stable in biological fluids. Thus, they have attracted scientific interest regarding their use as biomarkers for several diseases. miRNA-375 mainly influences β-cell function and insulin secretion. Several studies, primarily experimental, have assessed its role as a biomarker in type 2 diabetes, while recently obtained human evidence supports this potential role. Besides its diagnostic potential, miRNA-375 may also have therapeutic implications. In view of the growing epidemic of type 2 diabetes, there is an unmet need for identification of biomarkers for early recognition and monitoring of these patients. Long-term, prospective human studies are required to elucidate whether miRNA-375 can evolve as a key player in diagnosis and prognosis of type 2 diabetes.