BACKGROUND: The rising prevalence of obesity, as well as its detrimental effects on the brain, has drawn attention to specific dietary patterns. This study aimed to examine the effect of the Mediterranean-DASH Intervention for Neurodegenerative Delay (MIND) pattern on anthropometric parameters, hunger hormones, and brain structures in overweight and obese women. METHODS: This randomized trial was conducted in Shiraz between October 2018 and March 2019. We analyzed 37 healthy women with a mean age of 48±5.38 years and a Body Mass Index (BMI) of 32±0.69 Kg/m2. Participants were randomly allocated to a hypocaloric modified MIND diet or a hypocaloric control diet. Differences in anthropometric, laboratory analysis, and brain structure were determined at baseline and three-month follow-up. Data were analyzed using SPSS 22.0. Independent and paired sample t test were used to determine between and within differences. We also used mixed-model ANOVA to compare the mean differences between two-factor groups. RESULTS: A more significant weight reduction (P<0.0001), BMI (P<0.0001), percentage of body fat (P=0.03), waist circumference (P=0.01), and Leptin concentration (P=0.03) were found in the MIND diet group. The results also showed a significant increase in Ghrelin (P=0.002) and GLP-1 (P=0.01) levels in the MIND diet group. The findings revealed no differences in the whole and regional brain structures between the two groups. CONCLUSION: For the first time, this study showed that the MIND diet intervention could improve the devastating effect of obesity on metabolic profiles and anthropometric parameters. However, we could not find its effect on brain structures.Trial registration number: IRCT20190427043387N1.A preprint of this study was published at https://www.medrxiv.org/content/10.1101/2020.06.28.20142018v1.