Waterborne diseases pose a significant public health challenge in the Global South, attributed to inadequate access to clean water, insufficient sanitation infrastructure, and poor water treatment systems. These factors contribute to the contamination of water sources with microbial pathogens, placing individuals at a heightened risk of contracting waterborne diseases. Waterborne diseases in the Global South are caused by various bacterial pathogens, parasites, and viruses, with factors such as climate change, water scarcity, and human pollution influencing their proliferation. Vulnerable populations, including children, pregnant women, and immunocompromised individuals, bear the brunt of these diseases, resulting in preventable deaths and hindering socioeconomic development due to health-care costs. Traditional methods for combating these diseases have limitations, leading to the need for alternative water disinfection strategies, such as ultraviolet C light-emitting diodes (UVC LEDs). This review examines both the current state of waterborne diseases in the Global South (i.e., disease prevalence, causes, and public/systemic impacts) and the current landscape of UVC LED technology for water disinfection. Through the lens of this multi-focus review, we also explore the potential widespread implementation of UVC LED technology for water disinfection as a method of combating waterborne diseases to improve public health outcomes. Regulatory frameworks for UVC LED water treatment systems in the Global South remain limited. To address this limitation, we recommend an essential implementation framework that includes legislation, partnerships, sustainability, affordability, industrial and environmental standards, and robust evaluation protocols. Finally, we provide a substantial overview of the future directions and research opportunities in UVC LED technology and water treatment mechanisms aiming for promising public health outcomes. Embracing UVC LED technology can help address persistent disease challenges and improve public health in regions with limited infrastructure, thereby moving closer to achieving the United Nation’s Sustainable Development Goals and emphasizing the significance of universal access to improved WASH (safe water, sanitation, and hygiene) conditions.