Dietary approach is essential to obesity control, but the effectiveness of changes in meal frequency (MF) as strategies for loss and maintenance of body mass remain unclear. This study aimed to evaluate the influence of MF on a hypocaloric diet on weight loss, active ghrelin levels and metabolic indicators of women with obesity. This is a randomized, parallel clinical trial, including forty women, randomized in two groups, both following a hypocaloric diet, according to MF (G1 – six meals/day; G2 – three meals/day). Dietary, laboratory, anthropometric and body composition indicators were assessed, as well as energy expenditure (EE), before and after the 90 days of intervention. After intervention, both groups decreased body weight, body mass index (BMI), waist circumference, fat mass (FM), insulin and HOMA-IR. G1 increased insulin sensitivity and G2 reduced triglyceride and FM and increased fat-free mass (FFM). MF increased ghrelin levels. There were no differences in EE variables. Hypocaloric diet with different MF promoted a reduction in total weight, BMI, WC and FM and an improvement in glycidic metabolism. However, the accomplishment of the three meals/day increased the FFM and active ghrelin and reduced triglyceride, while six meals/day was more beneficial in increasing insulin sensitivity.