In the evolving digital landscape, Internet-based and mobile-based cognitive behavioral therapy (IM-CBT) has emerged as a pivotal modality for treating mental health disorders, particularly among individuals with chronic diseases. This chapter critically examines the effectiveness of IM-CBT in addressing both psychological and physical symptoms associated with chronic conditions. IM-CBT offers accessible, flexible, and cost-effective alternatives to traditional face-to-face CBT, addressing barriers such as potential stigma, long waiting time, and health disparities. The chapter categorizes IM-CBT into three modalities based on different ways of integrating therapeutic techniques and discusses their varying impacts on chronic disease. While evidence supports IM-CBT’s effectiveness in reducing anxiety, depression, and some physical symptoms, challenges such as standardization, patient adherence, and the integration of non-validated techniques warrant attention. The potential of using artificial intelligence for enhancing personalization and engagement is also explored, highlighting the need for further research to standardize protocols and improve patient outcomes. This chapter underscores the important complementary role of IM-CBT in traditional psychotherapies, particularly managing the complex interplay between physical and mental health in chronic disease populations.