Objectives: Chronic kidney disease (CKD) is a long-term disease, and to prevent it from developing from the early stage to the dialysis stage, patients follow the advice of their medical team. However, whether patients thoroughly understand the content of the health education that they are provided with and implement self-management to enhance their quality of life is worthy of research and investigation. Methods: This study employed a longitudinal research design and recruited 150 patients with CKD from a medical center in southern Taiwan. Structured questionnaires were used to collect their data a total of three times, and the data were analyzed using GEE. Results: The patients' average score on the short-form Mandarin Health Literacy Scale for CKD was 9.06 ± 3.205, and their self-management, overall quality of life, and eGFR demonstrated significant improvements over time. Conclusions: This study clarified long-term changes in the self-management and quality of life of patients with CKD. Medical teams are advised to provide diverse and proper care models to delay the deterioration of kidney function as well as prevent the need for dialysis in patients with CKD.