In this study, we used a cell model of non-alcoholic fatty liver and insulin resistance, namely PA-induced HepG2 cells, to prove the following finding for the first time: (1) Nifu decreases liver lipid accumulation and protects against NAFLD by enhancing fatty acid oxidation and reducing fatty acid production; (2) Nifu regulates glucose metabolism by inhibiting gluconeogenesis and activating glycogen synthesis; (3) Nifu alleviates PA-induced inflammatory responses and insulin resistance by modulating STAT3 signaling and the IL-6/STAT3/SOCS3 pathway. The gene discussed is SOCS3; the disease is metabolic dysfunction-associated steatotic liver disease.