Endometriosis is a complex disorder characterized by pain and infertility that, if not treated properly, it can disrupt the patient's quality of life and health significantly. The purpose of the study was to assess the effect of instructional supportive guidelines on alleviating endometriosis-related pain symptoms. Design: A quasi-experimental research design (non-equivalent group design) was utilized. Sample: A convenience sample of 100 women diagnosed with endometriosis. Settings: The study was conducted at Obstetrics and Gynecology outpatient clinics affiliated with Menoufia University Hospital and Shebin El-Kom Teaching Hospital. Instruments: Knowledge of mothers structured interviewing questionnaire, self-care practices' specific effect rating scale and numerical rating scale. Results: There was a highly statistically significant difference in total knowledge scores regarding the instructional supportive guidelines (92.0% & 97.0%) after implementing the guidelines. Also, there was a highly statistically significant decrease in the intensity of endometriosis-related pain in the study group (86.0 % -90.0%) compared to the control group. There was a highly statistically difference in the score of women's self-care practices for alleviating endometriosis-related symptoms after implementation of the guidelines compared to their self-care practices before it. Conclusion: The instructional supportive guidelines resulted in a highly statistically significant increase in the total knowledge scores, a decrease in the intensity of endometriosis-related pain symptoms. Recommendations: Instructional Supportive Guidelines should be provided for women with endometriosis to improve their quality of life and increase their awareness regarding the guidelines to decrease the endometriosis-related pain symptoms is necessary. Also, regular follow-ups should be done to detect any health problem.