Thinking is the fundamental methodology and core driving force to understand and reshape the world. Observing things， analyzing problems， resolving conflicts， and driving progress all require the guidance of a scientific mindset. Drug safety is a critical political， livelihood， economic， and social issue. In today’s era， drug production and distribution activities are becoming increasingly complex， and traditional regulatory approaches can hardly cope with today’s risks and challenges effectively.To comprehensively advance the scientific， law-based， internationalized， and modernized standards of drug safety work， it is essential to strengthen the political， scientific， law-based， and social mindset. This study respectively sorts out and focuses on analyzing the core essence， penetration of the rule of law， practical challenges and basic rules of various basic ways of thinking. It is necessary to have a vision and a deep consideration of drug safety supervision and scientific supervision， to strengthen the overall strategic planning； apply a political mindset as an anchor to ensure unwavering adherence to the core direction of drug safety； apply a scientific mindset to pursue objective truth， abiding by the scientific laws of drug safety regulation； apply a law-based mindset as standard to uphold rules and enhance law-based governance of drug regulation； apply a social mindset as catalyst to build synergy and foster social collaborative governance that proactively embrace the deeper changes in the future world and continuously breaks new ground in drug safety regulation.