AbstractIn traumatic brain injury (TBI) patients, a complex cascade of inflammatory responses are frequently observed following trauma. Numerous dietary agents have long been found to have potential in modulating inflammatory responses. This pilot study, designed an enteral formula with low inflammatory properties based on the dietary inflammatory index (DII®) and evaluated its effect on inflammatory and metabolic factors in critically ill TBI patients. This single‐blind randomized controlled pilot study was conducted at the Neurosurgical ICU of Shahid Kamyab Hospital (Mashhad, Iran). A total of 20 TBI patients were randomly assigned to receive either low‐DII score or standard formula at the intensive care unit (ICU). The primary outcomes of the study included clinical status, inflammatory biomarkers, APACHE II, SAPS II, SOFA, and NUTRIC scores. The trial groups did not differ significantly in baseline values. Following 14 days of intervention, there was a statistically significant decrease in the APACHE II, SAPS II, and NUTRIC scores and a significant increase in the GCS score in the low‐DII score formula group compared to the standard formula group. Over 2 weeks, high sensitivity C‐reactive protein (hs‐CRP) values of −2.73 (95% CI: −3.67, −1.79) mg/dL in the low‐DII score formula group versus 0.65 (95% CI: −0.29, 1.58) mg/dL in controls were obtained. Moreover, the length of hospital stay was longer for the standard formula group than for the low‐DII score formula group. The low‐DII score formula improves inflammatory factors (serum hs‐CRP) and metabolic biomarkers (LDL‐c and FBS). Furthermore, clinical outcomes, including the length of hospital stay and disease severity, appear to be enhanced.