Drug use and abuse among adolescents have always been concerning problem across the world. Since prevention is better than cure, avoiding the initiation of drug use and preventing from developing into drug abuse for adolescents are of crucial importance. Since kinds of prevention programs for drug use have been evaluated comprehensively, this paper first tires to review some evidence-based effective prevention programs in order to provide some reference for Macao, and then analyze the situation of adolescents’ drug problem, preventive measures that currently applied in Macao. TSSDM 2014 survey data is used for analysis. Results showed that the most effective anti-drug educational program is anti-drug activities from the perspectives of students. Besides, students’ anti-drug education experiences are positively correlated with their opposed attitudes towards substance use and perceived risk of drug use. Moreover, mediation analysis is also utilized to examine the relationship between anti-drug education experiences and their substance use behaviors, assuming that students’ opposed attitudes towards drug use and perceived risk of drug use are two mediating variables. It seems that students’ anti-drug education experiences have indirect effects on their substance use behaviors via those two mediators.