Administration of chicory polysaccharides (CP) can modify lipid metabolism, improve dyslipidemia, and reduce liver inflammation, all of which may help alleviate non-alcoholic fatty liver disease (NAFLD). However, the underlying mechanisms remain unclear. This study aimed to gain further understanding of the potential molecular mechanisms that mediate the protective effects of CP against NAFLD via transcriptomic and metabolomic analyses. Hepatic RNA-sequencing analysis demonstrated that long-term intake of CP restored expression of lipid metabolism-related genes Xbp1, Insig2, and Cth in NAFLD rats, thereby inhibiting de novo lipogenesis. Moreover, CP consumption restored expression levels of genes involved in pro-inflammatory responses, such as Irf1. In addition, metabolic data confirmed that CP treatment increased levels of L-palmitoylcarnitine and hexadecanoyl-CoA, implying that CP administration can promote hepatic fatty acid β-oxidation. The present results demonstrate the underlying mechanisms of CP in high-fat diet-induced NAFLD rats and suggest that CP treatment might provide a dietary therapeutic tool for the treatment of NAFLD in humans.