Obesity is a risk factor for metabolic disorders causes serious health problems and economic costs globally. Some Cirsium genus has been reported to possess anti-obesity effect and traditional uses for vascular diseases, anti-inflammatory and diuretic effects. This study aims to investigate the therapeutic value of endemic Cirsium species for obesity treatment. C. balikesirense Yildiz, Arabaci & Dirmenci (CB), C. nerimaniae Yildiz, Dirmenci & Arabaci (CN) and C. sommieri Petr. (CS) were selected for the study. High-fat diet (HFD) induced obese Sprague Dawley rats were employed for in vivo studies. The extract obtained aerial parts of Cirsium species were applied to rats orally for 8 weeks. To interpret the antiobesity activity, body weight of the rats were measured. Also, biochemical, histopathological and quantitative real-time PCR (RT-PCR) analysis were performed on rats. Bioactivity-guided fractionation studies were carried out guidance with in vitro lipase enzyme inhibition. The structures of the pure compounds purified using various chromatographic techniques were determined by spectroscopic methods. Oral administration of the extracts and orlistat decreased in body weights, adipocytes size, levels of serum low-density lipoprotein (LDL), triglyceride (TG), leptin levels, lipase, tumor necrosis factor-alpha (TNF-alpha), interleukin-1 beta (IL-1 beta), and increased levels of serum high-density lipoprotein (HDL), adiponectin. According to RT-PCR analysis, the extracts reduced the levels of key transcription factors in adipogenesis and fatty acid synthase (FAS). Bioactivity-guided fractionation studies led to isolation of active compounds as syringin, cimidahurinin, astragalin, afzelin, lupeol, and psi-taraxasterol. In conclusion, CB, CN, CS and their isolated compounds were uncovered to be hopeful as a candidate for antiobesity therapeutics. (C) 2021 SAAB. Published by Elsevier B.V. All rights reserved.