MicroRNA-26a (miRNA-26a) is a critical regulator of molecular processes, impacting the pathogenesis of numerous diseases due to its ability to modulate gene expression across various organ systems and tissues. This review examines the mechanisms of miRNA-26a action and its therapeutic potential, with a particular focus on its role in heart failure (HF). In HF, miRNA-26a exerts cardioprotective effects, suppressing cardiomyocyte hypertrophy, fibrosis, and electrical remodeling by targeting GATA4, CTGF, and KCNJ2. Reduced miRNA-26a expression correlates with HF progression, underscoring its role as a biomarker and therapeutic target. Interactions with other microRNAs, such as miR-1 and miR-133, amplify its effects. Beyond cardiology, miRNA-26a modulates oncological processes, e.g., inhibiting proliferation in colorectal cancer, inflammation in inflammatory bowel disease, and metabolic and neurodegenerative disorders by targeting EZH2, PTEN, and VEGF. Preclinical studies highlight the promise of miRNA-26a-mimics for HF treatment, though challenges in delivery and dosing warrant further exploration. This review article, with an emphasis on cardiovascular pathology, acknowledges the high prevalence and critical significance of HF in morbidity and mortality, advocating for research into combined strategies with other miRNAs. Overall, miRNA-26a holds significant potential for personalized medicine, offering improved outcomes for patients with HF and other related pathologies.