Background <p>MicroRNAs (miRNAs), small non-coding RNA molecules, are central players of post-transcriptional regulation of gene expression. miRNAs orchestrate various biological processes, such as cell proliferation, differentiation, immune homeostasis, and metabolic balance, by the fine-tuning of intracellular signaling pathways. Abnormal miRNA expression is associated with the pathogenesis of various multifactorial diseases, with diabetes mellitus and psoriasis being two classic paradigmatic conditions characterized by dysregulated miRNA function. Single-nucleotide polymorphisms (SNPs) in miRNA-coding genes may modify miRNA biogenesis, stability, and targeting, thus influencing susceptibility, severity, and response to therapy in diseases.</p> Objective <p>This review discusses prevailing evidence related to SNPs in miR-146a, miR-21, and miR-155, and their mechanistic contributions to the inflammatory, immunological, and metabolic pathways in diabetes and psoriasis.</p> Results <p>miRNA dysregulation through SNPs is an essential molecular pathway connecting immune dysfunction and metabolic imbalance. Modulation of these miRNAs presents exciting opportunities for precision therapy as well as diagnostics.</p> Conclusion <p>Combining SNP profiling with functional validation may make it possible to create personalized protocols for risk stratification, early detection, and customized treatment in diabetic as well as psoriatic patients.</p> Graphical abstract <p>miRNA–SNP crosstalk linking diabetes and psoriasis</p> <p></p>