This peer-reviewed article applies Peplau’s nursing theory to psilocybin-assisted therapy in hospice and palliative settings. Using a fictional cancer patient case, it shows how holistic nurse–patient communication can help individuals process grief, reduce anxiety, and find meaning during end-of-life care. By weaving therapeutic communication into preparation, dosing, and integration phases, the authors highlight how nurses play a vital role in making psychedelic therapy compassionate, ethical, and supportive.