This study aimed to assess the impact of spiritual care education on post-traumatic growth and resilience among patients diagnosed with leukemia. This randomized controlled trial study was conducted at Shahid Beheshti Hospital in Hamadan, Iran, in 2023. A total of 75 participants were recruited through convenience sampling and randomly assigned to either the intervention (N = 38) or control (N = 37) groups. Data collection included demographic information, the Post-Traumatic Growth questionnaire, and the Connor-Davidson Resilience Scale administered before, one month, and two months after the intervention. Participants in the intervention group received six sessions of spiritual care education, each lasting 30-45 min, with sessions spaced one day apart. Prior to the intervention, no significant differences were found in the mean scores of post-traumatic growth (P = 0.645) and resilience (P = 0.802) between the groups. However, following the intervention, significant between-group differences were observed in the mean scores of post-traumatic growth and resilience. For post-traumatic growth, the differences were statistically significant one month after the intervention (P < 0.001, d = 0.814), two months after the intervention (P < 0.001, d = 1.294), and overall (P < 0.001, η = 0.203). Similarly, for resilience, significant between-group differences were found at one month (P < 0.001, d = 1.078), at two months (P < 0.001, d = 1.023), and in the overall comparison (P < 0.001, η = 0.158). Moreover, within-group comparisons demonstrated a significant increase in post-traumatic growth (P < 0.001, η = 0.244) and resilience (P < 0.001, η = 0.200) scores from baseline to the final measurement in the intervention group. In contrast, no significant changes were observed in the control group for either post-traumatic growth (P = 0.795) or resilience (P = 0.539). These findings suggest that spiritual care education provided by nurses can contribute to psychological growth and resilience enhancement among leukemia patients, thereby promoting comprehensive care.