microRNAs (miRNAs) are small, non-coding RNA molecules that play crucial regulatory roles in numerous cellular processes. Recent investigations have highlighted the significant involvement of miRNA-122 (miR-122) in the pathogenesis of infectious diseases caused by diverse pathogens, encompassing viral, bacterial, and parasitic infections. In the context of viral infections, miR-122 exerts regulatory control over viral replication by binding to the viral genome and modulating the hosts antiviral response. For instance, in hepatitis B virus (HBV) infection, miR-122 restricts viral replication, while HBV, in turn, suppresses miR-122 expression. Conversely, miR-122 interacts with the hepatitis C virus (HCV) genome, facilitating viral replication. Regarding bacterial infections, miR-122 has been found to regulate host immune responses by influencing inflammatory cytokine production and phagocytosis. In Vibrio anguillarum infections, there is a significant reduction in miR-122 expression, contributing to the pathophysiology of bacterial infections. Toll-like receptor 14 (TLR14) has been identified as a novel target gene of miR-122, affecting inflammatory and immune responses. In the context of parasitic infections, miR-122 plays a crucial role in regulating host lipid metabolism and immune responses. For example, during Leishmania infection, miR-122-containing extracellular vesicles from liver cells are unable to enter infected macrophages, leading to a suppression of the inflammatory response. Furthermore, miR-122 exhibits promise as a potential biomarker for various infectious diseases. Its expression level in body fluids, particularly in serum and plasma, correlates with disease severity and treatment response in patients affected by HCV, HBV, and tuberculosis. This paper also discusses the potential of miR-122 as a biomarker in infectious diseases. In summary, this review provides a comprehensive and insightful overview of the emerging role of miR-122 in infectious diseases, detailing its mechanism of action and potential implications for the development of novel therapeutic strategies.