Dysfunctional hepatic metabolism has been linked to numerous diseases, including non-alcoholic fatty liver disease, the most common chronic liver disorder worldwide, which can progress to hepatic fibrosis, and is closely associated with insulin resistance and cardiovascular diseases. In addition, the liver secretes a wide array of metabolites, biomolecules, and microRNAs (miRNAs) and many of these secreted factors exert significant effects on metabolic processes both in the liver and in peripheral tissues. In this review, we summarize the involvement of liver-derived miRNAs in biological processes with an emphasis on delineating the communication between the liver and other tissues associated with metabolic disease progression. Furthermore, the review identifies the primary molecular targets by which miRNAs act. These consolidated findings from numerous studies provide insight into the underlying mechanism of various metabolic disease progression and suggest the possibility of using circulatory miRNAs as prognostic predictors and therapeutic targets for improving clinical intervention strategies.