Uranium extraction from seawater has been a topic of considerable interest over the past decades. However, Commercial facilities for uranium extraction from seawater have not yet been constructed due to its lack of economic feasibility. With the increasing demand for sustainable energy sources, there is a growing interest in eco-friendly uranium extraction methods. Despite this, the safeguards associated with these extraction techniques remain relatively under-researched, necessitating comprehensive studies that address both the economic feasibility and safeguards approach. The Korea Hydro & Nuclear Power Central Research Institute is poised to elucidate the economic value of uranium extraction from seawater and embark on research to extract Yellow Cake from seawater on a laboratory scale. Given these advancements, it becomes imperative to consider the approach to safeguards. In this study, a comprehensive review was conducted to understand the relevant regulations that encompass both international obligations in partnership with the IAEA and domestic guidelines, specifically the Nuclear Safety Act. Emphasis was placed on a detailed examination of the IAEA’s comprehensive safeguards agreement and its additional protocol, focusing on deriving the necessary regulatory timings, subjects, and methodologies for effective reporting and verification. We reviewed the safeguards guidelines and the IAEA policy to confirm the international non-proliferation obligations. The study also reviewed the impact of the State-Level Approach promoted by the IAEA and its implications on state-specific factors and evaluations of state technological advancement. Additionally, the regulatory aspects of extracted uranium as an internationally regulated material under the Nuclear Safety Act were critically assessed. In conclusion, this study explains the international and domestic regulatory considerations for uranium extraction from seawater. Ultimately, this study will provide valuable understanding for policymakers, researchers, and practitioners involved in uranium extraction from seawater. Additionally, we expect that this study will contribute to establishing the safeguards approach and regulatory framework for the commercialization of uranium extraction from seawater in the ROK.