This paper describes the relationship between Muslims and Christians in the middle period of Islamic history (1250-1850).  The two main points answered in this paper are, first; Relations between Muslims and Christians in the Era of Decline (1250-1500 AD) and, secondly, Relations between Muslims and Christians during the Three Great Kingdoms Period (1500-1800 AD). The method used is writing history, which includes heuristics, source criticism, interpretation, and historiography. The historical method is helpful for systematically and objectively reconstructing the past to reach a complete conclusion. The study results show that the relations between Islam and Christianity in the medieval period were more often confrontational than holding hands through a dialogical process. This period became critical for Muslims because it faced critical reciprocal tensions. Internally, Muslims are challenged to unite because of the diversity of cultures and the extent of their jurisdiction, and the excessive fanaticism of religious groups. While external challenges, the Abbasid dynasty faced attacks from the Mongols led by Hulagu Khan and Timur Lenk and attacks from the Safavid Empire in Persia. Specifically, the confrontational relations between Islam and Christianity were marked by the collapse of the Ayubbiyah Dynasty. Since then, Muslims and Christians have increased the scale of conflict known as the Holy War or Crusade.