Meal replacement plans are effective tools for weight loss and improvement of various clinical characteristics but not sustainable due to the severe energy restriction. The aim of the study was to evaluate the impact of meal replacement, specifically 388 kcal in total energy, on body composition and metabolic parameters in individuals with overweight and obesity from a Chinese population. A parallel, randomized controlled trial was performed with 174 participants (ChiCTR-OOC-17012000). The intervention group (N=86) was provided with a dinner meal replacement, and the control group (N=88) continued their routine diet as before. Body composition and blood parameters were assessed at 0, 4, 8, and 12 weeks. A post hoc analysis (least significant difference (LSD) test), repeated measurements, and paired T-test were used to compare each variable within and between groups. Significant (p < 0.001) improvements in body composition components were observed among the intervention group, including body weight (-4.3 ± 3.3%), body mass index (-4.3 ± 3.3%), waist circumference (-4.3 ± 4.4%), fat-free mass (-1.8 ± 2.9%), and body fat mass (-5.3 ± 8.8%). Body composition improvements corresponded with significant metabolic improvements of blood glucose (-4.7 ± 9.8%). Further improvements in visceral fat area (-7.7 ± 10.1%), accompanying with improvements in systolic (-3.7 ± 6.9%) and diastolic (-5.3 ± 7.7%) blood pressure, were only found in male subjects. To conclude, meal replacement intake with 388 kcal in total energy at dinner time for 12 weeks contributed to improvement in body composition and clinically significant metabolic parameters in both male and female participants with overweight/obesity. Additionally, glucose and blood pressure reduction were gender-specific highlighting the importance of gender stratification for design of nutritional intervention studies for improvement of health.