With the increasing exposure to and accessibility of drugs through online platforms, drug-related issues have become a growing societal concern. This study aims to identify effective communication strategies for drug prevention campaigns by employing an experimental approach based on the self-referencing effect and regulatory focus theory. This study adopts a 2 (reference type: self vs. other) × 2 (regulatory focus: prevention vs. promotion) between-subjects experimental design to investigate the influence of different message types on audience responses regarding fear arousal and risk perception. Findings indicate that prevention-focused messages significantly increase fear and personal risk perception, whereas promotion-focused messages induce comparatively lower levels of fear. In the case of social risk perception, regulatory focus played a crucial role, with a significant interaction effect observed between reference type and regulatory focus. Notably, gender differences emerged in responses to message types: male subjects exhibited a stronger reaction to prevention-focused messages with an other-referencing frame, whereas female subjects responded more strongly to prevention-focused messages with a self-referencing frame. These findings suggest that drug prevention message strategies may function differently depending on psychological characteristics and gender, offering practical implications for the design of effective public health campaigns.