Background <p>MiRNA not only participates in the occurrence of diabetes and its complications, but has also gradually become a new type of biomarker for dynamic prediction and risk stratification of diabetes.</p> Objective <p>This study aims to identify a novel diagnostic and predictive biomarker for type 2 diabetes mellitus (T2DM) and diabetic cardiomyopathy (DCM).</p> Methods <p>This study comprised three groups of subjects: a healthy controls group, a T2DM group and a DCM group. Serum levels of miR-378 were quantified using RT-qPCR. The diagnostic and predictive value of miR-378 in T2DM and DCM were assessed through Receiver Operating Characteristic (ROC)&#xa0;curve. The role of miR-378 in disease development was evaluated via the Chi-square test. Additionally, logistic regression analysis was employed to identify risk factors associated with DCM in T2DM patients. Additionally, A cellular model of DCM was constructed in vitro to explore the mechanism of miR-378's involvement in DCM.</p> Results <p>miR-378 levels were decreased in T2DM and DCM groups. miR-378 not only effectively discriminates between healthy individuals and T2DM patients but also serves as a prognostic indicator for the development of DCM in those with T2DM. The reduced expression of miR-378 emerges as an independent risk factor for T2DM individuals transitioning to DCM. Moreover, overexpression of miR-378 alleviated cardiomyocyte apoptosis, cardiomyocyte injury, and suppressed the secretion of inflammatory factors.</p> Conclusion <p>This study demonstrates that miR-378 serves as a potential diagnostic and predictive biomarker for T2DM and DCM. Decreased miR-378 levels increase the risk of DCM. Furthermore, the Overexpression of miR-378 alleviated cardiomyocyte damage and inflammation induced by high glucose. Consequently, miR-378 may be a potential therapeutic target for DCM.</p>