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Mycobacterium tuberculosis (Mtb) complex, responsible for tuberculosis (TB) infection, continues to be a predominant global cause of mortality due to intricate host-pathogen interactions that affect disease progression. MicroRNAs (miRNAs), essential posttranscriptional regulators, have become pivotal modulators of these relationships. Recent findings indicate that miRNAs actively regulate immunological responses to Mtb complex by modulating autophagy, apoptosis, and immune cell activities. This has resulted in increased interest in miRNAs as prospective diagnostic indicators for TB, especially in differentiating active infection from latent or inactive stages. Variations in miRNA expression during Mtb infection indicate disease progression and offer insights into the immune response. Furthermore, miRNAs present potential as therapeutic targets in host-directed therapy (HDT) techniques for TB infection. This work examines the function of miRNAs in TB pathogenesis, with the objective of identifying particular miRNAs that regulate the immune response to the Mtb complex, evaluating their diagnostic value and exploring their therapeutic implications in host-directed therapy for TB infection. The objective is to enhance comprehension of how miRNAs can facilitate improved diagnosis and treatment of TB., (© 2025 Wiley Periodicals LLC.)