Clinical and neuroscientific evidence indicates that transdiagnostic processes contribute to the generation and maintenance of psychopathological symptoms and disorders. Rigidity (inflexibility) appears a core feature of most transdiagnostic pathological processes. Decreasing rigidity may prove important to restore and maintain mental health. One of the primary domains in which rigidity and flexibility plays a role concerns the self. We adopt the pattern theory of self (PTS) for a working definition of self. This incorporates the pluralist view on self as constituted by multiple aspects or processes, understood to constitute a self-pattern, i.e. processes organized in non-linear dynamical relations across a number of time scales. The use of mindfulness meditation in the format of Mindfulness Based Interventions (MBIs) has been developed over four decades in Clinical Psychology. MBIs are promising as evidence-based treatments, shown to be equivalent to gold-standard treatments and superior to specific active controls in several randomized controlled trials. Notably, MBIs have been shown to target transdiagnostic symptoms. Given the hypothesized central role of rigid, habitual self-patterns in psychopathology, PTS offers a useful frame to understand how mindfulness may be beneficial in decreasing inflexibility. We discuss the evidence that mindfulness can alter the psychological and behavioral expression of individual aspects of the self-pattern, as well as favour change in the self-pattern as a whole gestalt.We discuss neuroscientific research on how the phenomenology of the self (pattern) is reflected in associated cortical networks and meditation-related alterations in cortical networks. Creating a synergy between these two aspects can increase understanding of psychopathological processes and improve diagnostic and therapeutic options.