Objective <p>The objective of this study was to compare the quality of life in patients with endometriosis undergoing treatment with progestins, OCPs, and GnRH agonists.</p> Methods <p>This prospective, observational, and comparative study was conducted on patients with endometriosis at Amir al-Momenin Hospital (Zabol, Iran) from 2022 to 2024. The Endometriosis Health Profile (EHP-30) questionnaire was used to utilized patients’ quality of life.</p> Results <p>The study included three groups of women using OCPs, progestins, and GnRH agonists, consisting of 39, 74, and 22 participants, respectively. No significant differences were observed among the three groups with regard to occupation, education, marital status, physical activity, coffee consumption, or tobacco and alcohol use. However, a number of significant differences were identified in nutritional status, dyschezia, and psychological disorders. No statistically significant differences were observed in quality-of-life scores among the three groups (<i>P</i> = 0.197).</p> Conclusion <p>The three treatment approaches demonstrated comparable outcomes in terms of the quality of life of patients diagnosed with endometriosis. However, the observed differences in certain demographic and psychological health variables underscore the necessity to consider factors beyond pharmacological treatment to enhance the quality of life in these patients.</p>