Objective We aimed to determine the effect of dienogest on cyst volume, symptoms, and quality of life in patients with endometrioma. Method This prospective cohort study included 37 patients diagnosed with endometrioma and planned for medical treatment. Subjects were treated with a 3-month oral dose of dienogest 2 mg/day. Pre-treatment and post-treatment endometriosis measurements were assessed via 3D ultrasonography, pain symptoms via 100-mm visual analog scale (VAS), and quality of life via Short Form-36. Results The mean age of the patients was 36.0 ± 6.6 years. The mean endometrioma volume was significantly reduced by 31% after treatment (26.7 ± 19.7 mm3) compared to the pre-treatment volume (17.4 ± 11.2 mm3, p < .001). Post-treatment VAS scores of dysmenorrhea, dyspareunia, and chronic pelvic pain VAS values were significantly decreased by 35.5% (p < .001), 37.5% (p < .001), and 38.5% (p < .001), respectively. The mean physical function score and mental health score significantly increased by 15% (p = .009) and 28% (p < .001), respectively. Conclusion Our findings showed dienogest treatment at oral doses of 2 mg/day for 3 months significantly reducing the size of endometrioma, reducing pain level, and increasing quality of life in women with endometriosis.