Polygonatum?sibiricum?is a traditional medicinal and dietary plant of the family?Liliaceae. The main functional?macromolecules?of?P. sibiricum?are?polysaccharides, which function in antioxidation and regulating immunity. Previous studies have shown that insulin resistance (IR),?oxidative stress, and inflammation are important factors in the induction of lipid?metabolic diseases?such as obesity. Therefore, in this study, we established a high-fat diet-induced rat model of obesity and?nonalcoholic fatty liver disease?(NAFLD) to explore the potential protective effect of?P. sibiricum?polysaccharides (PSPs) and the mechanisms behind it. After 4 weeks of high-fat diet feeding to induce obesity, the rats were treated with different doses of PSP solution or distilled water for 6 weeks. Compared with untreated obese rats, PSP-treated obese rats showed a decrease in body weight, serum?total cholesterol,?triglyceride, and low-density lipoprotein cholesterol levels, hepatic aspartate aminotransferase and?alanine aminotransferase?activity, hepatic?malondialdehyde?content, and hepatic levels of the pro-inflammatory factors tumor necrosis factor-α, interleukin-1β, and interleukin-6, as well as increased serum high-density lipoprotein cholesterol levels and hepatic?superoxide dismutase,?catalase, and?glutathione peroxidase?activity. Pathological analysis and?immunoblotting?of the liver tissues indicated that mechanistically, PSPs reduced obesity and NAFLD in rats by upregulating?insulin receptor?expression, increasing adenosine monophosphate-activated?protein kinase?phosphorylation, and downregulating sterol regulatory element-binding protein 2 and low-density lipoprotein receptor expression, thus promoting?lipid metabolism, decreasing body weight, and reducing inflammation and oxidative stress caused by?lipid accumulation. Based on these results, PSPs may have the potential to reduce obesity and NAFLD associated with a high-fat diet.