Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) is a leading cause of chronic liver disease affecting around 30% of adults worldwide, and its prevalence has increased in the last years. As a multisystem disorder, it involves various factors contributing to its development and progression. Management of MASLD focuses on lifestyle changes, such as diet and exercise, which can induce differential expression in microRNAs (miRNAs), small non-coding RNAs that play a key role in numerous signaling pathways linked to the pathophysiology of MASLD. While liver biopsy is essential for diagnosing MASLD, its invasiveness limits its use, prompting the need for less invasive methods. In this context, the main objective of this study was to advance in the use of circulating miRNAs as non-invasive biomarkers for the diagnosis and management of MASLD. This research had the following specific objectives: 1) Determine differences in circulating miRNA expression in subjects with overweight or obesity with MASLD compared to subjects with normal weight without MASLD. 2) Analyze circulating miRNA levels in subjects with overweight or obesity with MASLD and to establish associations with hepatic status during 2-year dietary intervention. 3) Examine the association between changes in circulating miRNA levels, inflammatory and biochemical markers, body composition and psychological status with changes in hepatic variables in subjects with overweight or obesity with MASLD during 2-year dietary intervention. 4) Build predictive models based on miRNAs, metabolic and psychological profiles, body composition, and liver status data for the diagnosis and management of MASLD in subjects with overweight or obesity. Regarding the first objective, circulating levels of miR122-5p, miR151a-3p, miR126-5p and miR21-5p were increased in MASLD group, and were associated with steatosis degree, hepatic fat content and liver stiffness. Regarding the second objective, the dietary intervention was able to modulate the expression of circulating miRNAs after 6, 12 and 24 months, obtaining different associations between miRNAs and hepatic status after nutritional intervention. Regarding the third objective, changes in circulating miR15b-3p were associated with changes in hepatic fat content after 6 and 24 months of intervention as well as changes in circulating miR29b-3p with changes in liver stiffness after 12 months. Regarding the fourth objective, the analysis revealed that the combination of miR151a-3p or miR21-5p with leptin had significant diagnostic accuracy for liver stiffness, miR151a-3p with glucose for hepatic fat content, and miR126-5p with leptin for steatosis. Additionally, the most effective panels for diagnosing MASLD after nutritional intervention consisted of the combination of miR15b-3p, miR126-5p and BMI after 6 months, miR29b-3p, miR122-5p, miR151a-3p and BMI after 12 months and miR21-5p, miR151a-3p and BMI after 24 months. Considering multiple factors, it was identified that the best panels for predicting MASLD were obtained after 24 months of intervention. The first included changes in liver stiffness, HDL cholesterol, BMI, depressive symptoms and TG, and the second, changes in hepatic fat, TC, miR15b-3p, TG and depressive symptoms. Circulating miRNAs can be used as non-invasive biomarkers to evaluate key aspects of MASLD and predict its presence after a nutritional strategy. It highlights the need to continue investigating and the potential development of combined panels to better understand disease progression and the effectiveness of nutritional interventions. In summary, these findings emphasize the role of miRNAs in the diagnosis and progression of MASLD, the importance of precision nutrition, and the need to adhere to healthy lifestyles.