Background <p>Health literacy is essential for safe and effective nursing practice, yet traditional teaching methods may not fully address students’ needs. This study evaluated a scenario-based interactive e-book integrating multimedia elements (e.g., videos, quizzes, and case-based activities) delivered through a digital learning platform to enhance nursing students’ health literacy performance.</p> Methods <p>A quasi-experimental design was conducted with 55 fourth-year nursing students from a Taiwanese university. Students were assigned to an experimental group (<i>n</i> = 28) that received a structured, instructor-guided e-book intervention within a course session or a control group (<i>n</i> = 27) that received traditional teaching. The 26-item Health Literacy Performance Scale, demonstrating strong validity and reliability, was administered three weeks before and immediately after the intervention. For educational parity, the control group accessed the e-book after data collection.</p> Results <p>Generalized Estimating Equations revealed no significant effects of time or time × group interaction. However, after adjusting for age, the main effect of group was significant (<i>p</i> = .015). Post hoc analysis showed that the experimental group scored higher on the post-test (<i>p</i> = .035), particularly in interpreting health education materials, assessing care needs, and correctly using medication, suggesting improved application of health literacy skills in clinical contexts.</p> Conclusions <p>Findings indicate that the scenario-based e-book effectively improved nursing students’ health literacy performance. This study highlights the value of integrating interactive, scenario-based digital learning tools into nursing education to support the development of practical communication and decision-making competencies.</p>