The aim of this study was to evaluate alterations in blood parameters after a low-carbohydrate high-fat (LCHF) diet in women with lipedema in comparison to overweight or obese women. A total of 115 women were classified into two groups: the lipedema group and the overweight/obesity group. Both study groups followed the caloric-restricted LCHF diet for 7 months. A total of 48 women completed the study. A reduction in body weight was observed in both study groups. A significant decrease in triglycerides and an increase in HDL-C concentrations were observed in both study groups. Despite the increase in the concentration of LDL-C observed in the lipedema group, changes in LDL-C differed between individual patients. Improvements in liver parameters, glucose tolerance, and a decrease in fasting insulin levels were observed, although they were less pronounced in the lipedema group than in the overweight/obesity group. Kidney and thyroid functions were similar before and after the LCHF diet in both groups. The LCHF diet may be a valuable nutritional strategy for lipedema and overweight/obese women, with a beneficial effect on weight, glucose profile, liver function, the concentration of triglycerides, and HDL-C and with no effect on kidney and thyroid function.