We aimed to investigate the effect of comprehensive nursing on the quality of life and levels of inflammatory cytokines in diabetic children. A controlled study was carried out with 58 diabetic children admitted to our hospital. According to the random number table method, patients were divided into the control group and the observation group, with 29 cases in each. Children in the control group were given routine nursing measures. Children in the observation group were given comprehensive nursing including psychology, health education, illness, diet and exercise, daily life, and humanistic care. After nursing, compared with the control group, the blood glucose indicators, self-rating anxiety scale, and self-rating depression scale score significantly decreased (P<0.05), while the drug-administration compliance, quality of life scores, and nursing satisfaction scores were significantly improved in the observation group (P<0.05). Additionally, we observed that the levels of nod-like receptor protein 3 (NLRP3) and interleukin-8 (IL-8) in the observation group were significantly decreased after nursing (P<0.05). Comprehensive nursing for diabetic children can effectively improve patients’ blood glucose, relieve negative psychology, and improve nursing satisfaction, which is worthy of recommendation and application.