<p>Sepsis-induced cardiomyopathy (SICM) is a life-threatening complication of sepsis, marked by temporary myocardial dysfunction. Emerging evidence highlights the critical roles of long non-coding RNAs (lncRNAs) and microRNAs (miRNA) in regulating the molecular pathways involved in SICM, including inflammation, oxidative stress, and apoptosis. These non-coding RNAs (ncRNAs) are increasingly recognized as valuable diagnostic and prognostic biomarkers, as well as promising therapeutic targets. This review explores the potential of lncRNAs and miRNA in SICM, focusing on their regulatory functions and therapeutic applications. Key miRNA, such as miRNA-495 and miRNA-21-3p, are highlighted as early diagnostic indicators and modulators of disease progression. Similarly, lncRNAs like MALAT1 and HOTAIR play crucial roles in controlling fibrosis and inflammation within the myocardium. Therapeutic strategies include the use of miRNA mimics to restore miRNA function, antagomiRNAs to inhibit overexpressed miRNA, and the modulation of lncRNA expression to mitigate SICM progression. Advanced delivery methods, including CRISPR/Cas9 gene-editing technology, are discussed as innovative approaches to enhance the specificity and efficacy of ncRNA-based therapies. In conclusion, ncRNAs offer significant potential as biomarkers and therapeutic agents in SICM, presenting new avenues for targeted treatment. However, further research is required to address challenges related to delivery, specificity, and long-term safety in clinical applications.</p> Graphical Abstract <p></p>