The inclusion of adolescents with Autism Spectrum Disorders (ASD) in mainstream environments, especially mainstream classrooms, is critically impeded by their difficulties in self-regulating their emotions. Albeit new technologies have shown tremendous emulation in the field of ASD, solutions to assist individuals with ASD in emotion regulation appear very limited. This paper addresses this critical challenge through the design and evaluation of a tablet-based application dedicated to supporting adolescents with ASD in self-regulating their emotions in mainstream inclusive classrooms. This system relies on well-proven (paper-based) emotion-regulation interventions reported by special-education teachers and families through a participatory design. The experiment included 14 adolescents with ASD (as well as 19 adolescents with Intellectual Disabilities) using the application during three months in mainstream schools. We compared these two groups with another group of 15 adolescents with ASD who were not equipped with our application. Usability performance as well as efficacy performance (emotion-regulation outcomes) have been investigated in situ. We showed that 1) our system is autonomously and successfully used in mainstream classrooms, 2) it is also an efficient support for adolescents with ASD to self-regulate their emotions. This paper demonstrates that emotion regulation of adolescents with ASD can be supported within mainstream classrooms through an assistive technology, in order to improve both behaviors and sociocognitive processes linked with core features of ASD. Moreover, it provides insights of a methodology suited to mainstream classrooms, building on previous research addressing specialized settings.