This study focuses on the activities of American missionaries in Kayseri, who found a large area of activity during the regression period of the Ottoman Empire. They mostly carried out educational and health activities in Kayseri Station, founded in 1854 as a part of the Western Anatolia Mission. In this study, the schools opened in Kayseri are mentioned in the section reserved for educational activities. In terms of such activities, American College in Talas is particularly important, and American missionaries efficiently founded hospitals in Kayseri within the framework of health services. Using American Board archive documents, the present study attempts to shed light on all activities carried out and gives brief information about missionary activities in Kayseri.