Oral administration of aqueous extracts of myoga (Zingiber mioga) alleviates fatty liver disease by decreasing liver weight and hepatic lipogenic gene expression in high-fat diet-fed mice. In the present study, we investigated whether aqueous myoga extract affects biomarkers of metabolic dysfunction-associated steatotic liver disease (MASLD) and insulin resistance-inducing hepatokines in human hepatocytes with MASLD features derived from humanized murine livers in vitro. The results showed that myoga extract decreased intracellular triglyceride content, leading to a reduction in leucine-rich α2 glycoprotein, an MASLD progression marker. Furthermore, myoga extract favorably modulated the secretion of hepatokines, suppressing insulin resistance-promoting hepatokines such as selenoprotein P, while enhancing the secretion of the beneficial hepatokine fibroblast growth factor 21. These findings demonstrated that the myoga extract restores hepatokine balance in MASLD-like hepatocytes in the PXB-cells LA model and facilitated the practical application of this regional specialty in advanced functional foods for the management of MASLD and related metabolic disorders.