Background/Objectives: Mental health issues among adolescents have increased during the pandemic necessitating targeted intervention programs. Improving health literacy (HL) of adolescents and parents could be a meaningful concept. This study aimed to explore the HL of parents and adolescents and its association with mental health screening outcomes in a bilingual region. Methods: A population-based anonymous online survey was conducted in South Tyrol, Italy. About 3,229 questionnaires provided information on HL and adolescents’ mental health concerns using standardized inter-nationally validated instruments. Parental and self-reported data were compared; the associations of HL with social support, problematic Internet use, language and mental health outcomes were explored. Results: Adolescents’ HL was associated with ques-tionnaire language, with better results observed for the German language (23.1% high HL) than for Italian (14.3%). Higher levels of HL among both parents and adolescents were related to better mental health outcomes in adolescents with higher associations to adolescents’ HL. Social support and problematic internet use were associated with both mental health outcomes and parental- and self-reported HL. HL accounted as a mediator partly for of the relationship between these two variables and self-reported mental health outcomes. Conclusions: Enhancing HL among parents and adolescents through school-based programs might be a promising strategy to improve adolescents’ mental health. In the bilingual context of South Tyrol, existing international German school-based programs can be adapted to fit the Italian health care and educational system. Further research is essential to evaluate the implementation of such programs and their effects on adolescents’ mental health and HL outcomes. South Tyrol offers the unique opportunity to apply German actual school HL knowledge and adapt it to Italian needs.