New psychoactive substances (NPS) are substances of abuse that easily evade existing controlled drug regulations. This study conducted a systematic review on controlled drug regulations and analyzed the numbers of new psychoactive substances (NPS) reported in six East and Southeast Asian countries in comparison to US and UK from 2009 to 2020. Generally, more NPS were reported in the US (551) and UK (400), compared to Japan (379), China (221), Singapore (142), South Korea (99), Malaysia (41), and Taiwan (35). Legislative mechanisms including the specific listing of individual substances, generic control of a family of substances, analogue control of similar substances, temporary bans of new substances were evaluated. In this review, countries that have adopted a combination of legislative mechanisms were able to identify higher numbers of NPS for regulatory control, such as the US, UK, Japan, Singapore, and South Korea. These findings can provide references to countries like Malaysia and Taiwan, to strengthen NPS-related regulations nationally. Countries in the East and Southeast Asian region should be encouraged to collaborate more closely and to implement additional legislative approaches most relevant to the regional NPS trends to bridge the regulatory gap and to prevent the spread of emerging NPS.