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Codium fragile (C. fragile) is a marine alga with high functional food potential. Recent studies have proven C. fragile extract (CFE) effective against obesity. However, the exact underlying mechanism of CFE's anti-obesity effects remains unclear. Herein, CFE was orally administered to male C57BL/6 mice for 7 weeks, along with a high-fat diet. CFE (100 mg/kg) effectively induced weight loss, lowered serum cholesterol levels, and suppressed adipocyte differentiation in white adipose tissue (WAT). Furthermore, CFE effectively reduced hepatic total triglyceride, cholesterol, and lipid levels, while significantly improving liver size and color. mRNA expression analysis in WAT and liver tissue revealed that CFE significantly suppressed the expression of PPARγ and aP-2 in adipocyte differentiation, and SREBP-1c and FAS in de novo lipogenesis, suggesting that CFE's anti-obesity effect is exerted by gene inhibition. PRACTICAL APPLICATIONS: Research on marine plants with anti-obesity effects has been increasing recently. This study demonstrated that C. fragile extract (CFE) is effective in reducing body weight and suppressing adipocyte differentiation, along with the improvement of fatty liver in mice fed with a high-fat diet (HFD). The anti-obesity effect of CFE was exhibited by the down-regulation of adipogenesis and lipogenesis, respectively. Based on these results, C. fragile could be useful, not only to effectively combat obesity but also in improving obesity-induced liver dysfunction., (© 2022 The Authors. Journal of Food Biochemistry published by Wiley Periodicals LLC.)