Background: Pain and infertility are hallmarks of endometriosis, a complex illness that, if left untreated, may have a devastating influence on a patient's life and health. The purpose of the study was to investigate the effect of instructional supportive guidelines on the quality of life among women with endometriosis. Design: The investigation was conducted using a design that was classified as quasi-experimental (non-equivalent group). Sample: 100 women diagnosed with endometriosis were selected as a convenience sample from a larger pool of women with the disease. Settings: Both Menoufia University Hospital and Shebin El-Kom Teaching Hospital (both in Egypt) participated in the research by providing access to their affiliated obstetrics and gynecology outpatient clinics. Instruments: A structured interviewing questionnaire, a numerical rating scale, and an endometriosis health profile questionnaire were used as the instruments in this study. Results: Total endometriosis knowledge ratings were drastically different of both groups, and this difference seemed extremely clinically meaningful after implementing the guidelines. In comparison to the control group, the pain associated with endometriosis was significantly less severe in the study group. This difference was statistically significant. The mean scores of the total endometriosis health profile showed impairment in quality of life in the study and control groups before the intervention. One and two months after the instructional supportive guidelines' implementation, the study group had a significantly lower mean total score of the endometriosis health profile than the control group, indicating improved quality of life. Conclusion: Increases in overall knowledge and decreases in endometriosis-related pain symptom severity were shown to be statistically significant outcomes of the instructional supporting guidelines. In addition, the women in the study group had a markedly better quality of life across all dimensions than those in the control group. Recommendations: It is vital to provide health education programs for women who have endometriosis to enhance their quality of life and expand understanding of the guidelines that may be followed in order to lessen the pain symptoms that are associated with endometriosis. It is also recommended that regular follow-up be performed in order to assess the level of health-related quality of life and identify any potential health issues at an early stage.