Background <p>Respect for life is a core component of medical humanities and professional identity. This study evaluated the effects of systematically integrating body/organ donation education into an anatomy course on medical students’ concepts of respect for life, explored underlying mechanisms, and examined whether the intervention affected academic performance.</p> Methods <p>An explanatory sequential mixed-methods design was used, combining a cluster randomized controlled trial (RCT) with qualitative inquiry. From February to July 2025, eight Systemic Anatomy classes (<i>N</i> = 336) at Hubei University of Medicine were randomized by class (1:1) to an intervention group (<i>n</i> = 169) or a control group (<i>n</i> = 167). The intervention group received an 18-week integrated teaching module on body/organ donation and respect for life; the control group received routine teaching only. Outcomes were measured at baseline (T1) and post-intervention (T2) using the Multidimensional Respect-for-Life Scale and other self-developed scales; 16 students in the intervention group completed semi-structured interviews.</p> Results <p>A total of 308 matched questionnaires were analyzed (intervention <i>n</i> = 155; control <i>n</i> = 153). Repeated-measures ANOVA showed a significant group × time interaction for the total respect-for-life score (F = 45.321, <i>P</i> &lt; 0.001, partial η²=0.136), with particularly robust gains in death cognition, gratitude and respect, and professional responsibility (all <i>P</i> &lt; 0.001). The intervention group also outperformed the control group in attitudes/intentions toward body donation and in incremental social responsibility and behavioral intention (Cohen’s d 1.686–1.746; all <i>P</i> &lt; 0.001). Qualitative analysis revealed an internalization pathway of “emotional engagement → cognitive reframing → behavioral empowerment → identity construction.” There was no significant between-group difference in final anatomy grades (<i>P</i> = 0.432).</p> Conclusions <p>Systematic integration of body/organ donation education into anatomy teaching effectively promotes medical students’ internalization of respect-for-life concepts and strengthens prosocial behavioral intentions without compromising academic achievement. This model provides empirical support for integrating ideological-political education and humanistic training into foundational medical curricula. Notably, this trial was retrospectively registered; therefore, the findings should be interpreted with this limitation in mind. Trial registration: Chinese Clinical Trial Registry, ChiCTR2600120733. Retrospectively registered on 19 March 2026.</p> Trial registration <p>This trial was registered with the Chinese Clinical Trial Registry (registration number: ChiCTR2600120733). It should be noted that the research team submitted the registration application on 15 August 2025, before the completion of data collection (which ended in July 2025). However, due to administrative processing delays at the registry center, formal approval was not granted until 19 March 2026. Consequently, the registration is retrospective relative to the study implementation period and does not comply with prospective registration guidelines. This limitation is acknowledged and discussed in the Limitations section.</p>