Here, we report that MPGI can effectively improve the hepatic steatosis and liver functions of high-fat diet (HFD)-fed mice by regulating multiple pathways, including gut microbiota homeostasis and the LPS/TLR4/NF-κB, AMPK/ACC/CPT1A, and AMPK/ULK1/LC3B signaling pathways. The gene discussed is NFKB1; the disease is fatty liver disease.