School is potentially one of the most important and effective agencies for the promotion of mental health. For this reason, in Italy, the Mental Health Department of The National Health Institute has developed an intervention based on a structured handbook. The aim of this intervention is to promote the psychological well-being of the students. In this study, we have evaluated the efficacy of this intervention through a quasi-experimental study design of four classes (two were control) of secondary education, including 79 students aged 14 to 16 years (15.35 ± 0.68). Assessments were administered before and after the intervention. The results showed improvement in perceived self-efficacy (p ≤ .001), emotional coping (p = .003), and overall well-being (p < .05). The students’ perception of usefulness was also increased (p < .05); the intervention successfully promoted the idea of life as a continuous process of learning, in change and growth (p < .05). The intervention was effective despite some limitations described by authors related to a lack of involvement of relatives and the team teachers, as well as the absence of homework; however, the adoption of a program promoting life skills, problem solving, and goal definition training is recommended with the use of a revised handbook.