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NAFLD progression can lead to cirrhosis and end\u2010stage liver disease. Hepatic kinase B1 (LKB1) is an upstream kinase of 5\u2032\u2010adenosine monophosphate\u2010activated protein kinase (AMPK), a crucial regulator in hepatic lipid metabolism. Activation of LKB1\/AMPK inhibits fatty acid synthesis, increases mitochondrial \u03b2\u2010oxidation, decreases the expression of genes encoding lipogenic enzymes, improves nonalcoholic steatohepatitis, and suppresses NAFLD progression. One potential opening for new and safe chemicals that can tackle the NAFLD pathogenesis through the LKB1\u2010AMPK pathway includes natural bioactive compounds. Accordingly, we summarized in vitro and in vivo studies regarding the effect of natural bioactive compounds such as a few members of the polyphenols, terpenoids, alkaloids, and some natural extracts on NAFLD through the LKB1\/AMPK signaling pathway. 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