AIM: To determine the role and efficacy of oral glutamine in the treatment of chemo-radiotherapy-induced oral mucositis and dysphagia in patients with carcinoma of the oropharynx and larynx. The primary objective of this study was to compare the incidence and severity of oral mucositis and dysphagia between the glutamine group (oral glutamine, along with concurrent chemo-radiotherapy) and the control group (concurrent chemo-radiotherapy alone, no glutamine). Secondary objectives were to compare the time to onset of oral mucositis and dysphagia, the incidence of treatment breaks (more than three consecutive radiation fractions missed), and significant weight loss (more than 3 kilograms of weight loss from the baseline) between the two groups. METHOD: A total of 60 patients with locally advanced carcinoma of the oropharynx and larynx (Stage III - IV) who were receiving concurrent chemo-radiotherapy were randomised to the glutamine group (study arm, n = 30) and the non-glutamine group (control arm, n = 30). All patients were treated by radiotherapy to a total dose of 70 Gy in 35 fractions, along with concurrent weekly injections of cisplatin (40 mg/m2) chemotherapy. Patients in the study arm received 10 gm of oral glutamine two hours before radiotherapy (five days a week during the seven-week course of radiotherapy). In the control arm, glutamine was not given to patients during the chemo-radiotherapy treatment. All patients were assessed for oral mucositis, dysphagia, weight loss, and compliance/gap in the treatment (greater than three consecutive days of radiation missed) until the completion of chemo-radiotherapy. Grading of oral mucositis and dysphagia was done as per the National Cancer Institute, Common Terminology Criteria for Adverse Events version 4.03. RESULTS: Out of 60 patients, 56 patients (93.33%) completed the full course of chemo-radiotherapy treatment. Twenty-seven patients (96.43%) in the control arm developed Grade III oral mucositis compared to only 12 patients (42.83%) in the glutamine arm (p < 0.001). Twenty-six patients (93%) in the control arm developed Grade III dysphagia compared to only 11 patients (39%) in the glutamine arm (p < 0.001). Glutamine significantly decreased the incidence and severity of mucositis and dysphagia. Glutamine delayed the onset of mucositis and dysphagia. As severe dysphagia was more prevalent in the control arm, feeding by Ryle's tube was required in 17 patients (56.67%) in the control arm versus only in eight patients (26.67%) in the glutamine arm (p = 0.03). Significant weight loss during the treatment was seen in all patients of the control arm (100% patients) compared to only 71% of the patients in the glutamine arm (p = 0.004). In the control arm, 46.67% patients had treatment interruption (gap) compared to 16.67% in the glutamine arm (p = 0.025). Sixteen patients (53%) from the control arm required admission (inpatient care) in the hospital to manage the treatment-toxicity (mucositis and dysphagia) compared to seven patients (23%) from the glutamine arm (p = 0.03). CONCLUSION: Glutamine significantly decreased the incidence and severity of chemo-radiotherapy-induced oral mucositis and dysphagia. It delayed the onset of oral mucositis and dysphagia, improved the compliance to the chemo-radiotherapy treatment, and reduced the requirement for hospitalization for the management of treatment-induced toxicities in patients with locally advanced carcinoma of the oropharynx and larynx.