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Lipoedema is a subcutaneous adipose tissue disease characterized by the increase in the amount and structure of fat mass (FM) in specific areas, causing pain and discomfort. 95% of patients fail to lose weight in the lipoedema areas. The study was conducted to evaluate body composition and general health status modification in a group of lipoedema patients (LIPPY) and a control group (CTRL) after four weeks of a modified Mediterranean diet therapy (mMeD). A total of 29 subjects were included in the data analysis, divided in two groups: 14 LIPPY and 15 CTRL. After the mMeD, both groups significantly decreased their weight and body mass index; the CTRL also showed a reduction of all the circumferences and all FM's compartments. LIPPY showed a decrease of FM in upper and lower limbs. No significant differences in Δ% between the groups were observed for the lean mass (LM). In LIPPY, an increase in the patients' ability to perform various daily physical activities related to the loss of arms' and legs' fat was observed. According to the European Quality of Life scale, the possibility for LIPPY subjects to perform simple daily activities with less fatigue, pain and anxiety is highlighted. Further long-term studies are recommended to confirm the mMeD as a good strategy for Lipoedema treatment.