This study explored the adoption, opportunities, and challenges of Digital Health Technologies (DHTs) in Decentralized Clinical Trials (DCTs) across India and Ireland. Using a mixed-methods approach, quantitative data were collected through surveys of clinical research professionals (n=133), and qualitative insights were gathered from five semi-structured interviews. The research revealed that Ireland demonstrated higher levels of DHT adoption, with more organizations reporting advanced or fully integrated systems, compared to India’s early-stage adoption and infrastructural limitations. Telemedicine platforms, remote monitoring devices, and mobile health apps were among the most widely used tools in both countries, although usage varied significantly. The COVID-19 pandemic acted as a key accelerator for DHT implementation in both the country. Real-time data collection, improved patient engagement, and reduced burden of site visits were identified as key benefits. However, significant challenges persist. In India, these included poor internet connectivity, digital illiteracy, and usability barriers, whereas Ireland’s primary challenges related to workforce training and data governance. Patients across both regions generally responded positively to DHTs, with younger participants showing greater comfort. Contract Research Organizations (CROs) were found to play a critical role in facilitating DHT integration, particularly in training, platform selection, and data management. The study concludes that region-specific strategies are needed to optimize DHT adoption—addressing infrastructure and training in India and enhancing interoperability and regulatory clarity in Ireland. Recommendations include investing in digital infrastructure, strengthening CRO partnerships, co-designing user-friendly platforms, and implementing public awareness campaigns. This research contributes comparative insights into DHT implementation in two regulatory environments and offers actionable guidance for stakeholders aiming to enhance the reach and efficiency of decentralized trials.