Background: Patients with inflammatory bowel disease (IBD) express a need for additional psychotherapy; however, psychological support is not incorporated in the routine care of persons with IBD. This systematic review aims to assess the effect of psychotherapy on quality of life (QoL). Methods: A systematic search was conducted on October 7, 2019, using Embase, Medline (Ovid), PubMed, Cochrane, Web of Science, PsycInfo, and Google Scholar to collect all types of clinical trials with psychotherapeutic interventions that measured QoL in patients with IBD aged ≥18 years. Quality of evidence was systematically assessed using the Grading of Recommendations Assessment, Development, and Evaluation criteria. Results: Out of 2560 articles, 31 studies (32 articles) were included with a total number of 2397 patients with active and inactive IBD. Of the 31 eligible studies, 11 reported a significant positive effect and 6 had ambiguous results regarding the impact of psychotherapeutic interventions on QoL. Treatment modalities differed in the reported studies and consisted of cognitive-behavioral therapy, psychodynamic therapy, acceptance and commitment therapy, stress management programs, mindfulness, hypnosis, or solution-focused therapy. All 4 studies focusing on patients with active disease reported a positive effect of psychotherapy. Trials applying cognitive-behavioral therapy reported the most consistent positive results. Conclusions: Psychotherapeutic interventions can improve QoL in patients with IBD. More high-quality research is needed before psychological therapy may be implemented in daily IBD practice and to evaluate whether early psychological intervention after diagnosis will result in better coping strategies and QoL throughout life.