Objective To investigate the effect of individualized nutritional therapy on the clinical outcome of perioperative patients with nutritional risks in digestive system diseases. Methods A prospective, randomized controlled clinical trial was conducted in 217 patients with digestive system diseases undergoing elective surgery, including 112 patients in the study group (receiving individualized nutritional therapy) and 105 patients in the control group (receiving non-individualized nutritional therapy). The baseline data, postoperative complications, hospital stay, hospital costs, postoperative mortality and improvement of the quality of life were recorded and compared. Results There were no differences in gender, age, education level, place of residence, payment method of medical expenses or nutritional risk screening (NRS) 2002 score between the two groups (all P>0.05). The incidence of postoperative infectious complications in the study group was lower than that in the control group (8.0%[9/112] vs 17.1%[18/105], P=0.042), while there were no differences in the incidence of total complications or non-infectious complications between the study group and the control group (15.2%[17/112] vs 22.9%[24/105], 7.1%[8/112] vs 5.7%[6/105], both P>0.05). The total hospital stay, postoperative hospital stay and total hospital costs of the study group were all lower than those of the control group (all P<0.05). There was no difference in postoperative mortality between the two groups (P=0.286). Multivariate logistic regression analysis showed that gender, NRS 2002 score and nutritional mode were the influencing factors of postoperative infectious complications (all P<0.05). Multiple stepwise regression analysis showed that the surgery type, NRS 2002 score and nutritional mode were the influencing factors of total hospital stay (all P<0.01), and age, nutritional mode and infectious complications were the influencing factors of postoperative hospital stay (all P<0.05). Surgical type, nutritional costs and total hospital stay were the influencing factors of total hospital costs (all P<0.05). Nutritional mode and total hospital stay were the influencing factors of nutritional costs (both P<0.01). There was no significant difference in European Organization for Research and Treatment of Cancer (EORTC) quality of life questionnaire-core 30 (QLQ-C30) scores between the two groups before discharge (58.9±17.1 vs 56.3±18.5) (P=0.631), but the scores of physical function, emotional function, fatigue and financial difficulty in the study group were all better than those in the control group (all P<0.05), and the score of nausea and vomiting was worse than that in the control group (P<0.05). Conclusion Individualized nutritional therapy can decrease the incidence of postoperative infectious complications, shorten the length of hospital stay, reduce the hospital costs, and improve the quality of life of perioperative patients with digestive system diseases.