This cluster randomized controlled trial (RCT) study conducted in Southern Finland investigates the effectiveness of a universal mindfulness-based intervention (MBI) in classrooms in improving emotional well-being and regulation among adolescents with elevated inattentiveness and/or hyperactivity-impulsivity. The study comprised 342 students, divided into an MBI group, a relaxation control group, and an inactive control group. Positive affect (PA) and negative affect (NA) and emotion regulation strategies (rumination, acceptance, catastrophizing, positive reappraisal, and self-kindness) were measured at pre- (T0), postintervention (T9), and 26-week follow-up (T26). The intervention effects were analyzed among all participants and by gender and symptom type. Compared to the controls, there was a beneficial effect for the MBI group in relation to acceptance at T9; acceptance remained at the baseline level in the MBI group but decreased in the inactive control group. Conversely, in the inactive control group, rumination decreased at T9, and positive reappraisal increased at T26 compared to the MBI group. The MBI had no other detectable effects. The results on emotion regulation strategies varied by gender. These findings do not provide convincing evidence that universal MBIs improve emotional well-being among students with elevated inattentiveness and/or hyperactivity-impulsivity. More research is needed to determine whether the programs are beneficial for all adolescents, regardless of mental health status.