Objective: To analyze the efficacy of Bifidobacterium triple viable bacteria tablets on neonatal necrotizing enterocolitis (NEC) and its impact on serum factors of the patients. Methods: From January 2021 to May 2025, 88 neonates with NEC admitted to our hospital were selected as study subjects. During the study, these 88 patients were evenly divided into two groups, namely the observation group and the control group, with 44 patients in each group based on the random number table method. In terms of treatment, the control group was treated with meropenem, while the observation group received additional treatment with Bifidobacterium triple viable bacteria powder based on the treatment plan of the control group. The clinical efficacy and differences in serum inflammatory factor levels between the two groups were compared. Results: The efficacy of the observation group (90.91%) was better than that of the control group (72.73%) (P < 0.05). After treatment, the levels of C-reactive protein (CRP) and procalcitonin (PCT) in both groups decreased compared to those before treatment, and the values of the above indicators in the observation group were lower than those in the control group (P < 0.05). Conclusion: Based on conventional treatment for NEC neonates, the use of Bifidobacterium triple viable bacteria tablets has significant efficacy and can effectively reduce serum inflammatory factor levels.