Background: Diabetic heart failure (DHF) poses a significant risk to cardiovascular health, particularly in individuals with diabetes, affecting their overall fitness and ability to engage in physical activities, including fitness players. The pathogenesis of DHF involves complex mechanisms such as cardiac hypertrophy, ventricular dilation, and compromised systolic function. This study aims to identify miRNAs related to DHF prognosis and unravel their molecular mechanisms in relation to DHF, with a specific focus on the implications for fitness players and their cardiovascular fitness. Methods: Public databases were searched for miRNA sequencing data from the peripheral blood of DHF patients, with further verification of expression levels conducted via qRT-PCR in patients' samples. Cellular proliferation was assessed using BrdU assays, while apoptosis, mitochondrial membrane potential (MMP), and reactive oxygen species (ROS) levels were evaluated through TUNEL staining and respective assays. Oxidative stress was measured by examining malondialdehyde (MDA) levels and superoxide dismutase (SOD) activity. Apoptosis-related markers were analyzed via Western blotting, and the interaction between miR-146a-3p and PPARα was confirmed through luciferase reporter assays. Results: Analysis of public datasets revealed a significant decrease in miR-146a-3p levels in DHF patients, correlating with patient survival rates. Overexpression of miR-146a-3p in high-glucose cultured H9C2 cells demonstrated its ability to bind and suppress PPARα, enhancing cellular proliferation and reducing apoptosis and oxidative stress. Furthermore, extracellular vehicles (EVs) loaded with miR-146a-3p showed potential in mitigating cardiac damage in DHF model rats, suggesting a novel therapeutic strategy that could be particularly beneficial for fitness players seeking to maintain or improve cardiovascular fitness in the face of DHF. Conclusions: MiR-146a-3p plays a crucial role in regulating myocardial cell apoptosis and oxidative stress by targeting PPARα, offering a promising approach to alleviate cardiac damage induced by high glucose levels. For fitness players, especially those with diabetes, miR-146a-3p represents a potential molecular target to enhance cardiovascular fitness and mitigate the risks associated with DHF. Further research is needed to explore the therapeutic applications of miR-146a-3p in improving cardiovascular health and performance in athletic populations.