Background: Cognitive flexibility is a core executive function often impaired in individuals with obsessive-compulsive disorder (OCD). Mindfulness-based interventions have been hypothesized to improve cognitive flexibility and may be a promising adjunctive intervention for adolescents with OCD. The current study examines which cognitive neurophysiological processes underlie mindfulness-based interventions in cognitive flexibility. Methods: In a randomized, interviewer-blind design, 76 adolescents (aged 10-19) with diagnosed or suspected OCD were enrolled. After exclusion, the final sample included 53 participants (45.3 % male). Participants were randomly assigned to either a mindfulness training group or an active control group (audiobook listening). Cognitive flexibility was assessed using a task-switching paradigm while EEG data were collected. Multivariate pattern analysis (MVPA) and source localization were applied to decomposed EEG data, enabling control of inter-individual variability. Results: The mindfulness group showed significantly reduced switch costs compared to the control group, indicating improved cognitive flexibility. The MVPA revealed group-specific decoding performance effects in fractions of EEG data reflecting response selection processes in a time window of 300-400 ms. In this time frame, the mindfulness group showed differential activation in the medial frontal gyrus and anterior cingulate cortex. Conclusions: This study provides evidence that an app-based mindfulness meditation training can enhance cognitive flexibility in adolescents with OCD through modulating stimulus-response selection processes in frontal cortices.