Fucoxanthin, a kind of exclusively algae-derived carotenoids, could reduce lipid content and regulate gut microbiota composition in obese mice, showing potential in preventing hyperlipidemia. This study aimed to illustrate fucoxanthin efficacy in modulating lipid metabolism in serum and liver of high-fat-induced hyperlipidemia mice, as well as investigate the underlying association with gut microbiota changes. Results showed that fucoxanthin significantly reduced body weight gain and body white fat of the mice. In the serum, total triglycerides (TG), total cholesterol (TC) contents were significantly decreased and high-density-lipoprotein cholesterol levels was significantly upregulated. Moreover, fucoxanthin remarkedly prevented lipid accumulation in the liver. Especially, metabolomics results showed that lipids and lipid-like molecules were significantly downregulated compared with the control, indicating the advance of hepatic lipid metabolism. Bile acids profile in the liver was also greatly changed by fucoxanthin. Meanwhile, fucoxanthin remodeled gut microbiota composition and promoted the relative abundance of Desulfovibrio, Blautia and Clostridia genera. Finally, correlation analysis revealed that these gut microbiota changes were closely related with hepatic metabolites/metabolism and serum lipids. Altogether, this study showed great potential of fucoxanthin in improving serum lipids profile, hepatic lipids and bile acids metabolism of hyperlipidemia mice, which was associated with gut microbiota alteration.