The disorders of gut-brain interaction (DGBIs) are a heterogeneous group of chronic conditions that greatly reduce patients' quality of life (QoL). To date, biopsychosocial factors (such as gastrointestinal symptoms, alexithymia, and interpersonal problems) are believed to contribute to the development and maintenance of DGBIs, but their role in affecting patients' QoL is still under investigation. Out of 141 patients seeking treatment for their gastrointestinal symptoms, 71 were diagnosed with a DGBI (47 females, 66.2%; Mage: 41.49 ± 17.23 years) and were age- and sex-matched to 71 healthy controls (47 females, 66.2%; Mage: 40.45 ± 16.38 years) without any current gastrointestinal symptom or diagnosis. Participants completed a sociodemographic and clinical questionnaire and a survey investigating several psychosocial risk factors. We found greater symptom severity and difficulties in identifying feelings among patients compared to controls. Further, multiple linear regression analyses evidenced that, among patients, higher expressive suppression of emotions, difficulties in identifying feelings and interpersonal problems, and a lower cognitive reappraisal of emotions predicted lower QoL. Data suggest that the QoL of patients with DGBIs is affected not only by common risk factors (e.g., interpersonal problems) but also by specific difficulties in processing and regulating emotions. The implications of these findings are discussed.