Background <p>Psychological empowerment is necessary for strengthening autonomy, motivation, and resilience among nurses in high-demand clinical settings. Neuro-linguistic programming (NLP), a behavioral approach that enhances cognitive flexibility and emotional regulation, may offer an effective pathway to internal empowerment. This study aimed to investigate the impact of an NLP-based educational intervention on nurses’ psychological empowerment.</p> Methods <p>A convergent mixed-methods, quasi-experimental study was conducted with 70 registered nurses at a private university hospital in Istanbul, Türkiye. Participants were randomly assigned to intervention (<i>n</i> = 35) and control (<i>n</i> = 35) groups. The intervention group completed a structured NLP program administered in five 3-h sessions over 1 week. Psychological empowerment was measured using the Psychological Empowerment Scale at three time points: pretest, immediate posttest, and 1-month follow-up. Data were analyzed using independent <i>t</i>-tests or Mann–Whitney U test for between-group comparisons and Friedman and Wilcoxon tests for within-group comparisons. To assess effect sizes, Cohen’s d was calculated. Qualitative data from pre- and post-intervention focus groups were analyzed via thematic analysis.</p> Results <p>The intervention group exhibited considerable improvements in total empowerment and all subdimensions—meaning, competence, self-determination, and impact—at posttest and follow-up (<i>p</i> &lt; .001). Effect sizes were very large: meaning d = 2.30, competence d = 3.12, self-determination d = 3.36, impact d = 1.44, and total score d = 1.84. Qualitative themes indicated increased perspective flexibility, role clarity, assertive communication, and goal-directed professional initiative following the training.</p> Conclusion <p>A structured NLP-based program substantially improved nurses’ psychological empowerment and related professional behaviors. Integrating NLP-informed strategies into staff development may offer a practical, scalable approach to foster autonomy, emotional self-regulation, and resilience in clinical nursing. Longer follow-up and multi-site trials are warranted.</p> Trial registration <p>The study was retrospectively registered in the ISRCTN registry under the number ISRCTN18008877 (Date of registration: July 7, 2025).</p>