The use of substances to improve sports performance is a widespread phenomenon among adolescents. Several anti-doping programs have been developed, mainly based on knowledge-based evidence. The main aim of the present study was to implement an anti-doping intervention in sports high school students, based on psychological framework, such as Socio-Cognitive Theory, through the development of a Serious Game (SG), i.e., a digital learning based on the game. The experimental design included an intervention group (n=167; F=37.7%; Meanage=17.5 years) and a control group (n=112; F=42%; Meanage=17.6). Both of groups completed the same questionnaire in two different occasions (i.e., time 1 and time 2), for measuring doping intention, self-regulatory efficacy to resist social pressure for the use of substances, moral disengagement, and doping knowledge. Data were analyzed through repeated measures of Group X Time ANOVA, demonstrating some degree of efficacy of the intervention, in particular, in terms of decrease of doping intention and the strengthening of doping knowledge. Moreover, we demonstrated that the score obtained during the implementation of the Serious Game partially could represent a coherent measure of the participants’ beliefs regarding doping. These results could be considered a starting point for future research to better develop technological anti-doping interventions.