Introduction: In the triennium 2023-2025, colorectal cancer (CRC) will be the third most common type of cancer in Brazil. The most used therapeutic approaches are chemotherapy (QTx) and radiotherapy (RTx). Chemotherapeutic agents, such as capecitabine, affect both malignant cells and normal cells such as gastrointestinal, capillary, and immune cells. Cellular damage in the gastrointestinal tract (GIT) results in various symptoms, such as mucositis and diarrhea. Diarrhea is linked to mucosal injury and can lead to dehydration, malnutrition, hospitalization, cardiovascular complications, and death. Mucositis, on the other hand, is inflammation that affects the GIT. This condition hinders treatment, leading to reductions, delays, or interruption of QTx. These scenarios impair the prognosis and quality of life of the patient, resulting in high costs for symptom control, nutritional support, management of secondary infections, and hospitalization. The Mucositis Study Group guidelines (MASCC/ISOO) recommend the use of probiotics as a preventive measure against diarrhea in cancer patients undergoing QTx and/or RTx. However, the safety of probiotic use in immunosuppressed patients is still controversial, and hypotheses are based on epidemiological and experimental studies. Therefore, it is necessary to evaluate whether supplementation with probiotics or symbiotics before chemotherapy would have the same beneficial results. Objective: The general objective of this study is to evaluate if symbiotic supplementation can reduce the incidence and severity of oral mucositis in cancer patients undergoing chemotherapy. Specific objectives include assessing the tolerability of supplementation, analyzing clinical and laboratory parameters related to mucositis, and investigating the impact of the intervention on the quality of life of patients. Methodology: This is a randomized, double-blind, parallel, single-center clinical trial to be conducted at the Borges da Costa Outpatient Clinic located at the Hospital das Clínicas of the Federal University of Minas Gerais in Belo Horizonte (HC-UFMG). Inclusion criteria involve adult patients, aged ≥ 18 years, of both sexes, diagnosed with colorectal cancer and candidates for first-line chemotherapy treatment with Capecitabine alone or in combination with Oxaliplatin, treated at HC/UFMG under the signature of the Informed Consent Form (ICF) and able to follow the research guidelines. The study was approved by the Research Ethics Committee of UFMG (CEP-UFMG) under protocol number CAAE 30177920.2.0000.5149. The study involves 80 participants distributed according to the chemotherapy protocol. Patients will be randomly divided into two groups designated as A and B: one control group receiving Maltodextrin, and the other intervention group receiving Symbiotic. The supplementation will be administered for 10 days, twice a day, before the start of chemotherapy treatment. Biological samples, such as feces and blood, will be collected for analysis of intestinal microbiota, short-chain fatty acid (SCFA) levels, presence of infection, intestinal permeability, and inflammatory markers. Biological collections will be performed at different time points throughout the study, including before supplementation (D0-D1), on the 10th day of supplementation (D10 pre-QTx), and on days 14 and 21 of the first chemotherapy cycle (D14-QTx and D21-QTx). Data will be collected through nutritional, anthropometric, and dietary assessments, including the Subjective Global Assessment (SGA), Anthropometric Assessment, Dietary Assessment (24h Recall and Food Frequency Questionnaire), as well as assessment of intestinal function and digestive complaints. Patients will be monitored daily, along with follow-up during treatment and data recording in the electronic medical record. Statistical analysis of the data will include sample size calculation, appropriate statistical tests, and an exploratory approach to evaluate clinical outcomes and study results. Expected Results It is expected that the results of this study will provide evidence on the efficacy of symbiotic supplementation in preventing oral mucositis in CRC patients undergoing chemotherapy. If the intervention proves to be effective, it could contribute to the development of more effective nutritional strategies in managing the side effects of oncological treatment, improving the quality of life and well-being of patients.