Background Post-stroke depression (PSD) is a neuropsychiatric sequela that causes serious adverse effects on the prognosis of stroke patients. Our developed iPad application is a very innovative approach designed to improve participants' depressive symptoms by presenting positive words stimuli in a video. Although this application has fewer side effects than existing pharmacological and non-pharmacological interventions and is likely less burdensome for patients and caregivers, its efficacy for PSD has not been investigated. Here we present a pilot randomized controlled trial (RCT) protocol to investigate the therapeutic potential of this application intervention for PSD patients. Methods This study is designed as a 5-week, single-center, open-label, parallel-group, pilot RCT. Thirty-two patients with PSD will be randomly assigned to a combination of the iPad application and usual rehabilitation or usual rehabilitation alone (1:1 allocation ratio). The iPad application intervention lasts 3 min a day, and the usual rehabilitation lasts 3 h a day. The primary outcome is the change from baseline in The Center for Epidemiologic Studies Depression Scale score at the end of the 5-week intervention. Discussion This pilot RCT is the first study to investigate the potential of iPad application interventions to reduce depressive symptoms in PSD patients. This pilot RCT determines whether this is a viable and effective intervention and informs the design for a full-scale trial. If our hypothesis is correct, this trial can provide evidence to augment the standard practice of iPad application interventions to improve depressive symptoms in patients with PSD.