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Background: Psychological factors contribute to the pathogenesis of functional dyspepsia (FD). Antidepressant agents are beneficial in treatment of refractory FD. However, their efficacy is greatly hindered by the poor treatment adherence. Stigma is present in patients with chronic diseases or mental disorders and could affect adherence. The present study was aimed to evaluate stigma prevalence in FD patients and to explore the impact of stigma on treatment adherence to antidepressants. Methods: Functional dyspepsia patients unsatisfied with the regular first‐line treatment and received newly initiated antidepressant medicine were recruited and subjected to antidepressant treatment for 8 weeks. Stigma scales and symptom scores of dyspepsia, depression, and anxiety were analyzed before and after treatment. Associations between stigma and medication adherence were evaluated. Key results: One hundred and ten of the enrolled 138 participants reported minimal disease‐related internalized stigma, and 28 reported mild stigma before antidepressant therapy. Male gender, lower education, and higher scores of dyspepsia, depression, and anxiety were predictors of stigma before treatment. The mean stigma scores increased after 8‐week antidepressant treatment. A proportion (36.4%‐89.9%) of patients showed stigma attached to antidepressant therapy in the 4‐question survey. Post‐treatment stigma scores negatively correlated with treatment adherence and efficacy. Patients with decreased post‐treatment stigma scores displayed better medication adherence and symptom improvement compared to those with elevated or unaltered post‐treatment stigma scores. Conclusions: Patients with refractory FD report stigma attached to the disease and antidepressants. It is an obstacle to treatment adherence and efficacy of antidepressant medication in FD therapy. [ABSTRACT FROM AUTHOR]