Introduction: Prevention of diverticulitis and diverticulitis-related complications is very important in patients with symptomatic uncomplicated diverticular disease (SUDD). The standard recommended practice is based on cyclic administration of rifaximin alpha. Objective: The objective of this study was to assess the effects of additional supplementation with a prebiotic consisting of soluble fiber arabinogalactan and lactoferrin in patients with diverticular disease receiving standard cyclic treatment with rifaximin alpha (Xifaxan 200 mg tablets at a dose of 2x400 mg for 7 days once a month in a cyclic regimen). Material and method: Patients were divided into two groups: group I (58 patients) received standard prophylaxis of diverticular disease exacerbation episodes with rifaximin alpha (Xifaxan 200 mg tablets) at a dose of 400 mg bid for 7 days in a cyclic regimen. Subjects in group II (63 patients) received the above regimen with the addition of a prebiotic containing soluble fiber arabinogalactan (5 g) and lactoferrin (50 mg) at a dose of 1 sachet per day for 3 months. The study was completed by 108 patients. Frequency of bowel movements, stool consistency, and incidence of pain were evaluated. Quality of life was measured using the Polish version of the Gastrointestinal Quality of Life Index (GIQLI) questionnaire. Other parameters under observation included complaints/symptoms possibly associated with the use of the study product (adverse effects), numbers of outpatient visits, hospitalizations and surgeries due to diverticular disease and complications of the disease. Patients were followed up for 3 months. Results: Significant reduction of pain and improvement in the quality of life was observed in both study groups. In addition, significant improvement regarding normalization of bowel movement frequency and stool consistency was observed in group II. The increase in the quality of life was significantly higher in group II patients as compared to patients receiving standard prophylactic treatment with rifaximin alpha alone (P = 0.00146). Conclusions: In patients with symptomatic uncomplicated diverticular disease, very good results can be obtained with the combined prophylactic therapy consisting of rifaximin alpha with prebiotic arabinogalactan and lactoferrin. Such a combination therapy minimizes the risk of exacerbation or complications and, at the same time, significantly improves bowel movements, reduces pain, and increases the quality of life.