Obesity is one of the health problems associated with FGF21 resistance. FGF21 is a hormone secreted in the liver and plays a role in energy homeostasis in adipose tissue. FGF 21 is used as an alternative for treating obesity. While the potential of H. sabdariffa for weight loss has been acknowledged, H. sabdariffa’s ability to handle FGF 21 is still unknown. This study aims to determine the potential of H. sabdariffa in FGF 21 resistance by measuring FGF 21 in adipose and liver tissue. This study was conducted at Biochemistry Animal House Laboratory at Faculty of Medicine Universitas Indonesia in January until May 2019. This experimental studies using 24 male rats for 6-10 weeks were divided into four groups, namely the normal control group (N), the obese control group (Ob), the obese group with H. sabdariffa dose 200 mg/kgBW/day (Ob-Hib 200), and obese groups with H. sabdariffa dose 400 mg/kgBW/day (Ob-Hib 400). H. sabdariffa is given every day for 5 weeks in a row. Examination of FGF21 protein in white adipose tissue and liver using the ELISA test. ANOVA test results showed an increase in FGF21 levels in adipose tissue in obese rats given H. sabdariffa extract dose of 400 mg/kgBW/day (p<0.05) and even significantly different than normal conditions (p<0.05). The results showed that a dose of 400 mg/kgBW had the potential to increase FGF21 levels in the liver (p<0.05). In conclusion, giving extract of H. sabdariffa has the potential for handling FGF21 resistance because H. sabdariffa is able to increase FGF 21 levels in adipose and liver tissue.