Pondok Pesantren, as one of the major boarding-based education systems in Indonesia, faces significant challenges in preventing and controlling infectious disease transmission. Huge number of students (santri), crowded dormitories, shared lavatories, limited healthcare facilities, and intense social interactions increase the risk of transmitting infectious diseases within the facilities. This study aims to provide initial assessment of the history of infectious diseases and the spread of infectious diseases among santri living in Pondok Pesantren before conducting training and intervention related to infectious diseases prevention and control programs. It is a quantitative study using a descriptive analysis approach conducted in July-September 2022 at Pondok Pesantren Assalafiyah 2 Mlangi. A non-probability sampling with total sampling of 848 santri was used. The data were collected using self-administered questionnaires developed on Google Form and imported to Microsoft Excel for further data analysis. The results indicate that the majority of the santri have a history of infectious diseases (90.7%) during their time living in Pondok Pesantren. The most common infectious diseases found were influenza (55.40%), scabies (20.94%), conjunctivitis (6.50%), varicella (6.11%), herpes simplex (2.21%), tuberculosis (1.39%), and measles (1.13%). During the COVID-19 pandemic, a total of 21.11% of the students had been exposed to COVID-19 and 98.47% of the students had received vaccinations. Considering these findings, it is essential for the staff and students living in Pondok Pesantren to understand the steps to prevent the occurrence of infectious diseases and be able to identify and provide initial treatment to stop the transmission of the disease. The development of digital health intervention using a website or application will be implemented to help the students report and consult case findings to medical experts.