Background: To date, surgeons and physicians have found positive results treating metabolic syndrome with surgical and non-surgical weight loss therapies. The purpose of this study was to evaluate changes in telomere length in patients with metabolic syndrome after weight loss., Methods/design: This study is a three-arm randomized controlled trial. The first group is composed of patients who have undergone stapleless bypass surgery (one anastomosis gastric bypass with an obstructive stapleless pouch and anastomosis (LOAGB-OSPAN)). The second group of patients underwent standard gastric bypass surgery (laparoscopic mini-gastric bypass-one anastomosis gastric bypass (LMGB-OAGB). The patients in the third group received non-surgical weight loss therapy, including a hypocaloric diet with energy restriction (- 500 kcal/day). The aim is to compare changes-telomere length, body mass index, comorbidities, and quality of life-in patients with metabolic syndrome after weight loss., Discussion: To the best of our knowledge, this is the first randomized study to simultaneously compare the effects of surgical and non-surgical weight loss on changes in telomere length. It could provide a solution to the growing problem of metabolic syndrome. Normalization of the body mass index results in improvements in the health of patients with metabolic syndrome., Trial Registration: ClinicalTrials.gov, NCT03667469 . Registered on 11 September 2018.