Background: Epilepsy is a disabling neurological disorder worldwide, affecting quality of life, which imposes a great burden on patients and their caregivers. Improving the quality of life is precisely one of the main objectives of therapeutic education, which are considered the gold standard in the delivery of health care. Aim: To evaluate the effect of a designed educational protocol on quality of life among patients with epilepsy. Design: A quasi-experimental research design using a one-group (pre-posttest) approach was used. Setting: The study was conducted at inpatient neurological department and outpatient clinics affiliated to Mansoura Main University Hospital. Subjects: A purposive sample of 100 patients diagnosed with epilepsy were selected. Tools: Four tools were used for data collection: Tool I: Structured interview questionnaire, Tool II: Knowledge assessment questionnaire, Tool III: Epilepsy self-management scale, and Tool IV: Quality of life in epilepsy inventory-31(QOLIE-31) scale. Results: There was a high statistically significance difference in the total mean score of knowledge, self-management practices, and quality of life pre and post implementing the designed educational protocol among the studied patients (p<.001). There was a significant positive correlation between the total score of knowledge, self-management practices among the studied patients and their quality of life at 3 and 6 months post implementing the designed educational protocol (p<.001& p=.006; p=0.022&p =0.041) respectively. Conclusion: The designed educational protocol proved that, there was an improvement in the knowledge and self-management practices total scores of the studied patients, which consequently had a positive effect on their quality of life. Recommendation: The designed educational protocol should be planned in a continuous manner and applied on regular basis to patients with epilepsy.