The increasing prevalence of metabolic disorders, often associated with high-fat diets (HFD), highlights the need for new therapeutic approaches, especially from natural sources. Dragon fruit pomace, a by-product of the fruit processing industry, is rich in polysaccharides with potential health benefits. This study investigates the effects of dragon fruit pomace-derived polysaccharides (PDPS) in alleviating HFD-induced metabolic dysfunction. Treatment with PDPS in mice fed a high-fat diet led to significant decreases in body weight increase, abdominal fat accumulation, total cholesterol, triglycerides, and low-density lipoprotein cholesterol (LDL-C) concentrations, along with a notable elevation in high-density lipoprotein cholesterol (HDL-C) concentrations. PDPS also improved glucose tolerance and prevented fat accumulation in the liver and adipose tissue. Additionally, PDPS exhibited anti-inflammatory properties, evidenced by reduced levels of pro-inflammatory cytokines (TNF-α, IL-1β, and IL-6) in the liver. Gut microbiota analysis indicated a shift toward beneficial bacteria, such as Romboutsia, Lachnospiraceae_NK4A136_group, Coriobacteriaceae_UCG-002, and Blautia. These findings suggest that PDPS may mitigate HFD-induced metabolic issues by enhancing lipid metabolism, glycemic control, and gut health, positioning it as a promising, sustainable functional ingredient for dietary interventions aimed at managing metabolic disorders.