The purpose of this investigation was to study the regulation effects of probiotics on intestinal adaptation in patients undergoing enteral nutrition treatment. In total 157 patients with enteral nutrition treatment were divided into study (n = 101) and control groups (n = 56) using random number table. In this study a double-blind, randomized controlled trial was carried out. The basal energy expenditure (BEE) was calculated based on Harris-Benedict formula (nitrogen supply was 0.2 g/(kg·d)). The study group was given enteral nutrition and probiotics and the control group was given enteral nutrition alone. The experimental period was 10 days. We recorded basic demographic data and clinical information, observed body weight (kg) and body mass index (BMI) (kg/m2) at 0 and 10 days after enteral nutrition, and evaluated nutritional and metabolic status in the major organs such as intestine and kidney. Malnutrition was improved in both groups. On the 10th day after enteral nutrition treatment, plasma-albumin (ALB) and prealbumin (PA) in both groups were higher than those before treatment (P < 0.05). Compared with intestinal tolerance, the incidence of diarrhea in the study group was 10.9% (11/101), which was significantly lower than that (23.2%, 13/56) in the control group (P < 0.05), but the total incidence of single symptoms such as abdominal distension, abdominal colic, nausea, vomiting and diarrhoea was 45.5% in the study group and 53.6% in the control group, with no significant difference (P > 0.05). There were no significant differences between the two groups in body weight, BMI, NRS2002 nutritional risk score, acute physiology and chronic health evaluation (APAACHE)-II the cause and starting time of enteral nutrition, blood glucose (BG), serum creatinine (Cr) or blood urea nitrogen (BUN) (P > 0.05). Probiotics significantly improve intestinal adaptation in patients with enteral nutrition treatment, being conducive to the clinical application of enteral nutrition.