Objective: To explore the application effect of the hospital-community-family model-based combined rehabilitation exercise intervention on middle-aged and elderly patients with chronic kidney disease. Methods: Using the convenience sampling method, 80 patients in the stable stage of CKD who were treated in the nephrology department of a tertiary hospital from May 2022 to June 2023 were selected as the research subjects. They were divided into the experimental group (40 cases) and the control group (40 cases) by random number table method. The control group received conventional exercise intervention plus telephone follow-up, while the experimental group received combined hospital-community-family model-based exercise intervention in addition to the control group, using remote medical guidance and monitoring of the application effect of exercise rehabilitation on middle-aged and elderly patients with chronic kidney disease. The glomerular filtration rate, 6-minute walking distance, fatigue and social support scores of the two groups of patients were measured before the intervention, 4 weeks after the intervention, and 12 weeks after the intervention. Results: Before the intervention, there were no statistically significant differences in glomerular filtration rate, 6-minute walking distance, fatigue and social support scores between the two groups (P>0.05). After 12 weeks of intervention, the glomerular filtration rate, 6-minute walking distance and social support scores of the experimental group were higher than those of the control group; the differences were statistically significant (P < 0.05). The behavioral, emotional, sensory and cognitive scores of the Piper-Fatigue Revised Scale of the experimental group were lower than those of the control group, and the differences were statistically significant (P<0.05). Conclusion: Based on the hospital-community-family model combined rehabilitation exercise, using remote medical guidance for the continuous care of middle-aged and elderly patients in the stable stage of chronic kidney disease can effectively improve the exercise endurance and social support level of patients, improve the fatigue condition, and the implementation effect is positively correlated with the intervention time.