This dissertation project scrutinizes how approaches to different knowledge systems changed between 1650 and 1800 in Western Europe and the Ottoman Empire. Through analyzing parallel histories of how Europeans understood Ottoman knowledge culture, and how Ottomans perceived European epistemology and which elements were emphasized within ongoing diplomatic and cultural interaction, this dissertation captures how emerging epistemologies were integrated into existing ones in both contexts. European and Ottoman scholars of the mid-seventeenth century associated this intellectual feat with the quest for "universality" on a common ground of religious "skepticism." This ideal of "universal knowledge" imbued with "skepticism" created scholarly networks in Constantinople. During the late seventeenth century, European scholars criticized humanist discourse on the Ottomans and Islamic culture, and suggested revising this tradition through attention to works by contemporary Ottoman scholars. In a similar vein, Ottoman scholars looked for European sources that could help them transcend their knowledge limits. Despite this mutual interest between Ottomans and Europeans, their intellectual exchanges were highly uneven and selective since these networks revolved around a few Sufi Ottoman scholars who had "heterodox" approaches to Islamic knowledge cultures. By the mid-eighteenth century, mainstream European epistemology began to disregard any form of Islamic epistemologies. Understanding Islam was no longer a means of obtaining "universal truth." However, European epistemology became the basis of the pursuit of "objective truth" in both European and Ottoman contexts which led to disputes over the relation between science and Islam in the Ottoman Empire. This project explores why and how this shift occurred through analyzing the entanglement of epistemologies and its crucial role in creating modern science.