Background: Lipedema is a chronic and progressive adipose tissue disorder that causes significant morbidity and negatively influences mental health and quality of life, and increases the risk of depression, anxiety, and eating disorders. One construct of relevance to better understanding psychological disorders is emotion regulation (ER). Therefore, the aim of this study is to investigate the difficulties in ER among lipedema patients compared to healthy people without lipedema. Methods: This cross-sectional study assessed differences in ER and anxiety between two groups: 26 female patients with lipedema and 26 sex- and age-matched healthy controls. The Difficulties in Emotion Regulation Scale (DERS) assessed emotional regulation across six dimensions: Impulse control, goal-directed behavior, awareness, clarity, non-acceptance, and strategies. Anxiety was assessed by the Hamilton Anxiety Scale (HAM-A). ANOVA assessed differences in measures between lipedema and healthy control groups. Results: Lipedema patients presented with significantly more difficulties in ER and a higher level of anxiety than those without lipedema. Specifically, the lipedema group showed higher and significant differences in total DERS and anxiety scores and all DERS subscales scores compared to those without lipedema. Conclusions: Lipedema patients showed significant difficulties with ER, and were associated with anxiety symptoms, indicating that ER difficulties may play a role in developing emotional disorders, such as anxiety, for patients with lipedema. The health care provider should pay more attention to ER difficulties and psychological status among lipedema patients.