A randomized controlled trial was carried out to assess the effectiveness of a manual therapy protocol in terms of the clinical characteristics, quality of life, and emotional condition of the women with endometriosis-related pelvic pain. Forty-one women (mean age of 36.10 (6.97) years) with pelvic pain due to endometriosis were randomly divided into (i) a manual therapy group (MTG) (n= 21) and (ii) a placebo group (PG) (n= 20). Both groups received an 8-week intervention. Pain, lumbar mobility, endometriosis health profile, quality of life, depression and anxiety levels, and the patient’s perception of change were assessed before (T0) and after (T1) the intervention, as well as at a one-month follow-up (T2) and a six-month follow-up (T3). The MTG significantly improved pain intensity, powerlessness, lumbar mobility, and physical quality of life at T1 (p< 0.05). The results were maintained for pain intensity at T2 and T3. In addition, both the MTG and PG improved emotional wellbeing at T1 (p< 0.05). Neither group improved in terms of social support, self-image, and depression and anxiety levels after the intervention (p> 0.05). In conclusion, manual therapy may be an excellent complement to the gynecological treatment of endometriosis-related pelvic pain by alleviating pain and improving women’s endometriosis health profile and physical quality of life.