Fucosylated chondroitin sulfate (fCS) and its depolymerized derivative (DfCS), prepared from sea cucumbers, are well-known for their anticoagulant activity. However, their other functional activities are poorly understood. Recently, we obtained fCS oligosaccharides from Isostichopus Badionotus by a modified controllable Fenton-system, named as DfCS-Ib. The functional activities of these oligosaccharides are still unclear. The present study investigated anti-hyperlipidemic activity of DfCS-Ib using a high-fat diet (HFD)–fed mice model. The results indicated that DfCS-Ib reduced obesity, hyperlipidemia, and inflammation caused by HFD. Meanwhile, DfCS-Ib increased the mRNA expression of PPARγ and decreased the mRNA expression of leptin, aP2, and F4/80 in fat tissue. Transcriptome analysis indicated that DfCS-Ib normalized the expressions of genes regulating lipid metabolism. Our results suggested that DfCS-Ib can alleviated lipid disorder by reducing lipid synthesis and promoting lipid lipidolysis. DfCS-Ib can act as a functional agent to regulate lipid disorder.