〔Abstract〕 Objective To investigate the effects of glutamine supplementation on inflammation and intestinal barrier function in patients with severe head injury (SHI). Methods A total of 94 cases of SHI patients admitted to the First People's Hospital of Chenzhou from June 2018 to December 2020 were selected and divided into two groups according to their medical records,with 47 cases in the control group and 47 cases in the observation group. All patients received conventional treatment and early enteral nutrition, while the observation group received glutamine in nutrient solution. The clinical treatment efficiency of the two groups, as well as the nutritional levels, inflammatory factors, intestinal barrier function and complications were compared between the two groups on the 14th day of treatment. Results The total effective rate of the observation group was 82.98%, which was significantly higher than 61.70% of the control group (P < 0.05). After 14 days of treatment, the levels of albumin (ALB), serum total protein (TP), transferrin (TRF) and the score of Glasgow Coma Scale (GCS) in two groups were significantly increased compared with those before treatment, while upper arm muscle circumference (AMC) and triceps skin fold thickness (TSF) in the control group were significantly decreased compared with those before treatment. The differences were statistically significant (P < 0.05). After 14 days of treatment, ALB, TP, TSF, TRF, AMC and GCS scores in the observation group were higher than those in the control group, the differences were statistically significant (P < 0.05). After 14 days of treatment, the levels of soluble triggering receptor-1 (sTREM-1), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) in the two groups were significantly decreased compared with those before treatment, and the levels of sTREM-1, IL-6 and TNF-α in the observation group were lower than those in the control group. The differences were statistically significant (P < 0.05). On the 14th day of treatment, the levels of diamine oxidase (DAO), procalcitonin (PCT) and D-lactic acid in the two groups were significantly decreased compared with those before treatment, and the levels of DAO, PCT and D-lactic acid in the observation group were lower than those in control group, the differences were statistically significant (P< 0.05). The incidence of gastrointestinal discomfort and pulmonary infection in the observation group was lower than that in the control group, the differences were statistically significant (P < 0.05). Conclusion The addition of glutamine to enteral nutrition in SHI patients can protect the structure and function of intestinal mucosal barrier, inhibit the release of inflammatory mediators, and reduce complications and infection.