In response to growing environmental concerns, the scientific community is increasingly incorporating green chemistry principles into modern analytical techniques. Electrochemical paper-based analytical devices (ePADs) have emerged as a sustainable and efficient alternative to conventional analytical devices, offering robust applications in point-of-care testing, personalized healthcare, environmental monitoring, and food safety. ePADs align with green chemistry by minimizing reagent use, reducing energy consumption, and being disposable, making them ideal for eco-friendly and cost-effective analyses. Their user-friendly interface, alongside sensitive and selective detection capabilities, has driven their popularity in recent years. This review traces the evolution of ePADs from simple designs to complex multilayered structures that optimize analyte flow and improve detection. It also delves into innovative electrode fabrication methods, assessing key advantages, limitations, and modification strategies for enhanced sensitivity. Application-focused sections explore recent advancements in using ePADs for detecting diseases, monitoring environmental hazards like heavy metals and bacterial contamination, and screening contaminants in food. The integration of cutting-edge technologies, such as wearable wireless devices and the Internet of Things (IoT), further positions ePADs at the forefront of point-of-care testing (POCT). Finally, the review identifies key research gaps and proposes future directions for the field.