The current study evaluated a theoretically-derived model of the relationships between psychological traits (neuroticism and mindfulness) and gastrointestinal (GI) symptom burden with indirect effects via general dispositional cognitions and health-related cognitions. A sample of women (N = 210, Mage = 22.83, SDage = 9.78) completed an online questionnaire battery consisting of self-reported GI symptom burden, neuroticism, mindfulness, general cognitions (emotional intelligence, reappraisal, suppression, rumination), and health-related cognitions (gastrointestinal-specific anxiety, pain catastrophizing). Our hypotheses were tested using multiple regression, latent variable, and structural equational modeling. Both mindfulness (Beta = − .220, p = .011) and neuroticism (Beta = .234, p = .001) significantly independently predicted GI symptom burden. Additionally, these relationships were completely accounted for via indirect effects of general cognitions and health-related cognitions, supporting our hypotheses: Indirect effect of neuroticism on GI symptom burden: Beta = .228, p = .007; Indirect effect of mindfulness on symptom burden: Beta = − .308, p = .011. The findings from the current study highlight the important role of both general and health-related cognitions in the experience of GI symptom burden and support theoretical models that posit mechanisms of mindfulness via adaptive coping strategies. Given the subjective nature of symptom experience, these findings may help to explain the efficacy of psychological therapies in reducing GI symptom burden.