Dysmenorrhoea is a condition where there is pain or cramps in the abdomen that can interfere daily activity and reduce quality of life. These pain and cramps may be due to increased prostaglandins. Calcium serves to reduce pain and cramps during menstruation. Vitamin B6 and vitamin D can help to reduce anxiety levels in premenstrual syndrome. The purpose of this study was to determine the effect of calcium combination supplement on dysmenorrhea pain and quality of life of the respondents. This research use quasy experimental method. A total of 70 students of Faculty of Medicine and Health Sciences of Muhammadiyah University of Yogyakarta who suffered from Dysmenorrhoea pain were divided into 2 groups: the control group that did not get treatment and the test group that received treatment which was to consume supplement combination of calcium, vitamin B6, vitamin D, and vitamin C in the form of effective Protecal Solid® effervescent tablets administered on the 15th day of the menstrual cycle until the first day of menstruation. The measurement with the VAS pain scale and BPI quality of life was performed on the 15th day of the menstrual cycle and the first day of menstruation. Data were analyzed using paired sample t test and independent sample t test. The result of the analysis with independent sample t test showed that there was a decrease of VAS pain scale in control group and treatment group with decreasing for 0.80±1.64 and 1.74±1.52 consecutively (p-value 0,015<0,05). The results obtained from BPI value analysis were improved quality of life in treatment group compared to the control group with consecutive result 3.20±0.79 and 1.80±0.49 (p-value 0,002<0,05). Supplement combination of calcium, vitamin B6, vitamin D, and vitamin C administration in the form of Protecal Solid® effervescent tablets can reduce the scale of pain and improve quality of life in women with Dysmenorrhoea.