Background: Emergency department (ED) nurses are routinely exposed to high-stress clinical environments, increasing their risk for burnout and emotional exhaustion. In holistic nursing, self-care is viewed as a professional and ethical responsibility essential to delivering whole-person care. This pilot study, guided by the Integrative Nursing Framework, explored the use of a mobile mindfulness app as a holistic intervention to support nurse well-being. Purpose: To explore how ED nurses experience and manage stress and burnout and to evaluate the effects of a mobile mindfulness app on these outcomes. Methods: An explanatory sequential mixed-methods design was used. Eleven ED nurses used the Headspace app for 4 weeks and completed pre- and post-intervention surveys measuring perceived stress, burnout, mindfulness, and well-being. Nine participants also completed post-intervention interviews. Quantitative data were analyzed using Wilcoxon signed-rank tests; qualitative data were analyzed using thematic analysis. Results: Perceived stress significantly decreased, while mindfulness and well-being significantly increased. Burnout scores showed no significant change. Themes included usability, personal impact, barriers to engagement, and recommendations for improvement. Conclusions: This study demonstrates the feasibility of mobile mindfulness as a holistic, self-directed intervention that aligns with holistic nursing values and supports ED nurses’ well-being in demanding care environments.