Evidence from trials demonstrating the benefits and risks of low-glycemic index and fat-restricted diets in weight loss and blood lipid profile changes is unclear. This study aimed to assess the implemented and effects of a fat-restricted low-glycemic index diet on weight control and blood lipid profile changes in in overweight/obese Southwest Chinese individualst.This prospective pilot study enrolled overweight/obese subjects at the People's Hospital of Sichuan Province between February and July 2019. The daily energy intake was reduced by 300 to 500 kcal according to the participant's weight and activity level, with low-glycemic index carbohydrate- and fat-energy ratios < 45% and 25% to 30%, respectively. Participants received guidance for 3 months by telephone follow-up, internet interaction, or WeChat. Changes in weight, body composition, and blood profile were measured.A total of 254 patients were finally analyzed, including 101 males and 153 females. After adjusting for potential confounders, weight (P < .001), body mass index (P < .001), waist circumference (P < .001), waist-hip ratio (P < .001), body fat percentage (P < .001), visceral fat area (P < .001), basal metabolism (P = .002), cholesterol (P < .001), and triglycerides (P < .001) were significantly reduced after the 3-month intervention. The above indexes showed no significant differences between men and women.Regardless of gender, fat-restricted low-glycemic index diet might be helpful for controlling weight and lowering blood cholesterol and triglycerides in overweight/obese individuals in Southwest China.