Purpose <p>This study aims to assess the adherence and safety of the home-based exercise program in patients with aplastic anemia (AA) who are undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT). Additionally, it aims to determine whether this program can enhance patients’ quality of life (QoL), alleviate fatigue, increase exercise tolerance, and reduce psychological stress.</p> Methods <p>This study involved 80 patients with AA from the Hematology Department of a comprehensive tertiary hospital. All participants met the British Committee for Standards in Haematology (BCSH) diagnostic criteria, were aged 18–65&#xa0;years, and had undergone allo-HSCT within the past 1–12&#xa0;months. All patients were enrolled within 100&#xa0;days post-transplant discharge. The control group received standard exercise nursing care, while the intervention group completed a 12-week home-based exercise program. Adherence and safety were monitored during the intervention, and QoL, fatigue level, exercise tolerance, and psychological distress were assessed at baseline (<i>T</i>0), week 4 (<i>T</i>1), week 8 (<i>T</i>2), and week 12 (<i>T</i>3).</p> Results <p>Exercise adherence exceeded 70%, with no adverse events reported. Repeated measures analysis revealed that QoL scores and 6MWD increased over time for both groups. At weeks 4, 8, and 12 of the intervention, the experimental group exhibited significantly higher QoL scores and 6MWD compared to the control group, with the differences being statistically significant. Both groups demonstrated a decrease in fatigue and psychological distress scores as the intervention progressed. At weeks 4, 8, and 12, the experimental group reported significantly lower levels of fatigue and psychological distress than the control group, with these differences also reaching statistical significance and a small to moderate effect size.</p> Conclusions <p>Home-based exercise is feasible for patients with AA undergoing allo-HSCT and showed an improvement in QoL, fatigue, exercise tolerance, and psychological status, which can serve as an effective adjuvant therapy during the post allo-transplant rehabilitation process.</p> Implications for Cancer Survivors <p>This study provides a new perspective and method for the long-term rehabilitation of AA patients following allo-HSCT.</p>