Crataegus pinnatifida is the dried fruit of Crataegus pinnatifida. Crataegus pinnatifida polysaccharides (CPPs) eluted with water as the mobile phase (CPPs-H-1) is one of the important active components. CPPs-H-1 has anti-oxidation and blood lipid regulation activities in vitro. Therefore, we investigated the effects of CPPs-H-1 on nonalcoholic fatty liver disease (NAFLD) in C57/BL6J mice. As a result, CPPs-H-1 inhibited the rapid growth of body weight and alleviated the liver injury caused by high-fat diets, significantly reducing the liver index and blood lipid levels in the model group, inhibiting the production of inflammation and cytokines, and inhibiting oxidative stress. CPPs-H-1 also enhanced intestinal barrier function. At the phylum level, CPPs-H-1 reduced the ratio of Firmicutes to Bacteroides (F/B) and regulated the content of short-chain fatty acids (SCFAs). The CPPs-H-1 may regulate intestinal flora composition, and improve intestinal barrier function, ultimately delaying the progression of NAFLD in mice. Also, CPPs-H-1 improved NAFLD progression by enhancing the Amp-activated protein kinase (AMPK)/peroxisome proliferator-activated receptor α (PPARα) signaling pathway to enhance fatty acid oxidation. All these results confirm that CPPs-H-1 plays a multi-pathway and multi-target role in the improvement of NAFLD.