Metabolic dysfunction–associated steatotic liver disease (MASLD) is the commonest form of liver disease and includes a wide spectrum of liver injury. Metabolic dysfunction–associated steatohepatitis (MASH) represents the progressive form of this liver disease, caused by a persistent pro-inflammatory condition promoted by an obesogenic environment and peripheral insulin resistance. When lipid-driven inflammation and oxidative stress are perpetuated over years, the enhanced fibrogenesis process causes an excessive scar tissue formation that may lead to advanced forms of liver disease. There is no current pharmacological treatment for MASLD and lifestyle interventions are unsatisfactory. Mesenchymal stem cell–derived extracellular vesicles (EVs) have shown a potential application in the MASLD field in preclinical studies on murine models. In fact, EVs have shown the ability to convey enzymes or noncoding RNA to target specific cell populations and regulate their activity to modulate liver injury and fibrosis. In this chapter, we summarize the key pathophysiological pathways involved in the onset of MASLD and review the current available studies on the application of stem-cell derived exosomes in chronic liver disease.