Irritable bowel syndrome (IBS) is a common gastrointestinal disorder with significant negative impacts on quality of Life. This study aimed to investigate the relationships between psychosocial factors, cognitive distortions, and quality of Life in individuals with IBS and the mediating role of cognitive distortions. Participants were 200 female students of king Khalid University with IBS who completed self-report measures of psychosocial factors, cognitive distortions, and quality of Life and The Rome III Diagnostic Questionnaire for Irritable Bowel Syndrome (Rome III). Results showed that perceived stress, anxiety, depression, and cognitive distortions were negatively associated with quality of Life. Furthermore, cognitive distortions partially mediated the relationships between psychosocial factors and quality of Life. These findings highlight the importance of addressing psychosocial factors and cognitive distortions in treating IBS. Cognitive-behavioral therapy may be an effective treatment approach for reducing stress, anxiety, and depression and challenging cognitive distortions in IBS patients.