Objective <p>Cystic fibrosis (CF) is a fatal hereditary disorder that leads to respiratory infections and gastrointestinal inflammation with possible association with intestinal dysbiosis. The present study was conducted with the aim of investigating the effects of probiotic consumption in improving pulmonary, gastrointestinal, and growth symptoms in patients with CF.</p> Materials and methods <p>In this double-blind randomized clinical trial, 110 CF patients were examined. Patients were divided into two equal groups of 55 subjects. Patients in the probiotic group consumed Lactobacillus reuteri at the rate of 10⁸ CFU/d for one month, and the control group received a placebo. Then, pulmonary, gastrointestinal, and growth-related outcomes as well as quality of life were assessed after one month of intervention as well as at three-month follow-up.</p> Results <p>The results of our study showed that in both intervention and control groups, weight increases significantly after 12 weeks (<i>P</i> = 0.01). However, no remarkable difference was reported between the two groups after 12 weeks (<i>P</i> = 0.09). In addition, no significant changes were observed between the two groups after 4 and 12 weeks regarding BMI and FEV1. Based on the findings, the score of the CFQ questionnaire in the intervention group increased significantly in the 4th and 12th week. No significant differences were observed between the two groups in terms of factors related to lung function or exacerbations after 12 weeks.The only notable effect reported was related to pain attacks in the probiotic group compared to the placebo group after 4 weeks (<i>P</i> = 0.02).</p> Conclusion <p>In general, treatment with probiotics improved the quality of life in patients with CF. However, no significant effect was observed on pulmonary, gastrointestinal, and growth-related outcomes.</p> Trial registration <p>This study was retrospectively registered IRCT registration number: IRCT20240105060622N1 (Registration date: 2024-08-16).</p>