Anxiety is one of the most common psychiatric comorbidities in people with epilepsy and often involves fears specifically related to the condition, such as anxiety related to the fear of having another seizure. These epilepsy- or seizure-related fears have been reported as being more disabling than the seizures themselves and significantly impact quality of life. Although research has suggested that exposure therapy (ET) is helpful in decreasing anxiety in people with epilepsy, no research to our knowledge has been conducted on ET in people with epilepsy using virtual reality (VR). The use of novel technologies such as an immersive VR head-mounted display for ET in this population offers several benefits. Indeed, using VR can increase accessibility for people with epilepsy with transportation barriers (eg, those who live outside urban centers or who have a suspended driver's license owing to their condition), among other advantages. In the present research protocol, we describe the design of an innovative VR-ET program administered in the home that focuses on decreasing anxiety in people with epilepsy, specifically anxiety related to their epilepsy or seizures. Our primary objective is to examine the feasibility of the study protocol and proposed treatment as well as identify suggestions for improvement when designing subsequent larger clinical trials. Our secondary objective is to evaluate whether VR-ET is effective in decreasing anxiety in a pilot study. We hypothesize that levels of anxiety in people with epilepsy will decrease from using VR-ET. This mixed methods study comprises 3 phases. Phase 1 involves engaging with those with lived experience through a web-based questionnaire to validate assumptions about anxiety in people with epilepsy. Phase 2 involves filming videos using a 360° camera for the VR-ET intervention (likely consisting of 3 sets of scenes, each with 3 intensity levels) based on the epilepsy- and seizure-related fears most commonly reported in the phase 1 questionnaire. Finally, phase 3 involves evaluating the at-home VR-ET intervention and study methods using a series of validated scales, as well as semistructured interviews. This pilot study was funded in November 2021. Data collection for phase 1 was completed as of August 7, 2022, and had a final sample of 18 participants. Our findings will add to the limited body of knowledge on anxiety in people with epilepsy and the use of VR in this population. We anticipate that the insights gained from this study will lay the foundation for a novel and accessible VR intervention for this underrecognized and undertreated comorbidity in people with epilepsy. ClinicalTrials.gov NCT05296057; https://clinicaltrials.gov/ct2/show/NCT05296057. DERR1-10.2196/41523.