BackgroundBoth low‐carbohydrate (LC) and calorie-restricted (CR) diets have been shown to have metabolic benefits. However, the two regimens have yet to be thoroughly compared. We conducted a 12-week randomized trial to compare the effects of these diets separately and in combination on both weight loss and metabolic risk factors in overweight/obese individuals.MethodsA total of 302 participants were randomized to LC diet (n= 76), CR diet (n= 75), LC + CR diet (n= 76), or normal control (NC) diet (n= 75) using a computer-based random number generator. The primary outcome was the change in body mass index (BMI). The secondary outcomes included body weight, waist circumference, waist-to-hip ratio, body fat, and metabolic risk factors. All participants attended health education sessions during the trial.ResultsA total of 298 participants were analyzed. BMI change over 12 weeks was − 0.6 (95% CI, − 0.8 to − 0.3) kg/m2in NC, − 1.3 (95% CI, − 1.5 to − 1.1) kg/m2in CR, − 2.3 (95% CI, − 2.6 to − 2.1) kg/m2in LC, and − 2.9 (95% CI, − 3.2 to − 2.6) kg/m2in LC + CR. LC + CR diet was more effective than LC or CR diet alone at reducing BMI (P= 0.001 andP< 0.001, respectively). Furthermore, compared with the CR diet, the LC + CR diet and LC diet further reduced body weight, waist circumference, and body fat. Serum triglycerides were significantly reduced in the LC + CR diet group compared with the LC or CR diet alone. Plasma glucose, homeostasis model assessment of insulin resistance, and cholesterol concentrations (total, LDL, and HDL) did not change significantly between the groups during the 12-week intervention.ConclusionsThe reduction of carbohydrate intake without restricting caloric intake is more potent to achieve weight loss over 12 weeks when compared to a calorie-restricted diet in overweight/obese adults. The combination of restricting carbohydrate and total calorie intake may augment the beneficial effects of reducing BMI, body weight, and metabolic risk factors among overweight/obese individuals.Trial registrationThe study was approved by the institutional review board of Zhujiang Hospital of Southern Medical University and registered at the China Clinical Trial Registration Center (registration number: ChiCTR1800015156).Supplementary InformationThe online version contains supplementary material available at 10.1186/s12916-023-02869-9.