To investigate the effects of different weight loss interventions on body mass index (BMI) and glucose and lipid metabolism in obese patients. Obese patients (n = 135) admitted to our hospital between December 2020 and August 2022 were divided into 3 groups, according to their diet patterns: calorie-restricted diet (CRD) group (n = 39), high-protein diet (HPD) group (n = 28), and 5 + 2 intermittent fasting (IF) group (n = 68). Body weight, body fat rate, BMI, hip circumference, and waist circumference were measured before and 60 days after implementation of the respective diet plan. Glycosylated hemoglobin (HbA1c), fasting blood glucose (FBG), 2h postprandial blood glucose (2hPG), triglyceride (TG), total cholesterol, low-density lipoprotein, high-density lipoprotein, and adverse events were evaluated. Following the dietary intervention, the weight (P = .005 for CRD, P < .001 for HPD, and P = .001 for IF), body fat rate (P = .027 for CRD, P = .002 for HPD, and P = .011 for IF group), BMI (P = .017 for CRD, P < .001 for HPD, and P = .002 for IF group), hip circumference (P < .001 for CRD, P = .013 for HPD, and P = .032 for IF group), waist circumference (P = .005 for CRD, P < .001 for HPD, and P = .028 for IF group), HbA1c (P = .014 for CRD, P = .002 for HPD, and P = .029 for IF group), FBG (P = .017 for CRD, P < .001 for HPD, and P = .033 for IF group), and 2hPG (P = .009 for CRD, P = .001 for HPD, and P = .012 for IF group), were significantly decreased. TG (P = .007 for CRD, P < .001 for HPD, and P = .018 for IF group), TC (P = .029 for CRD, P = .013 for HPD, and P = .041 for IF group), LDL-C (P = .033 for CRD, P = .021 for HPD, and P = .042 for IF group), and LDL-C (P = .011 for CRD, P < .001 for HPD, and P = .027 for IF group) improved significantly in the 3 groups, when compared to that before treatment. The HPD had the best effect on reducing blood lipids, followed by the CRD; the effect of IF was slightly lesser. Short-term HPD, CRD, and IF can reduce the weight and body fat of overweight/obese individuals and improve blood lipid and blood sugar levels. The effect of HPD on weight loss, body fat, and blood lipid levels was greater than that of CRD or IF.Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.