Type II diabetes is considered a chronic disease that influences the affected person's quality of life and imposes a high economic burden on the patient and society. The enhancement of health literacy seems essential for self-management and disease control in patients with type II diabetes. Consequently, this study was performed to evaluate the cost-effectiveness of enhanced health literacy in type II diabetes patients. This study was of quantitative and economic evaluation type. A population of 232 patients was selected among those referred to the Tafihan Shiraz clinic based on the quality of entry and exit. The health literacy educational intervention was carried out for three months. In order to collect information, researchers used the SF36 questionnaire and the checklist of costs. The Cost Effectiveness Ratio (CER) and Incremental Cost Effectiveness Ratio (ICER) were calculated. Moreover, the costs of each unit of increasing the quality of life before and after the intervention were calculated. A decision was made to determine the cost-effectiveness of the intervention. According to the results, 40% of the participants were females, and 34.5% were 30-40 years old. Examination of the quality of life in patients before the intervention indicated that the mean and standard deviation of the patients' quality of life before the intervention was 18.43±44.99, and the mean and standard deviation of the quality of life after the intervention was 49.57±16.21. Moreover, the patients' quality of life increased after the educational intervention. The total direct medical costs were $717,484 and $685,620 before and after the intervention, respectively. The total indirect medical costs were $604,122 and $493,011 before and after the intervention, respectively. Moreover, the total indirect costs were $122,535 and $122,119 before and after the intervention, respectively. The study was cost-effective with CER=0.9 and ICER= - 140,000 per increase in the quality of life. Improving health literacy can have a range of benefits and improve the quality of life of patients with type II diabetes and reduce their treatment costs, and thereby, this may be seen as an effective step toward the recovery of patients with type II diabetes.