Background Parental bereavement after loss of a child is often more profound and prolonged than grief experienced in other context of other losses and associated with an increased risk for long-term psychological and physical morbidities. Aim To explore the effectiveness of “unity-oriented psychology concepts instruction” on reducing depression and increasing spiritual well-being in bereaved mothers. Method A single-subject study was conducted on three bereaved mothers who lost their children to cancer in Mahak hospital during last 6 to 12 months ago. Each person participated in six (90-minute) individual session of the unity-oriented psychology concepts instruction. Data were collected the using the questionnaire of Beck depression inventory-II and spiritual well-being scale( Paloutzian & Ellison 1982) for eight times( three times at the baseline phase, three times at the intervention phase, and two times at the follow-up phase). The collected data were analyzed by indicators of process changes and calculate the recovery percentage. Results The results showed a significant decrease on depression and increase on spiritual well-being compared to the baseline and the most amount of decrease and increase was observed in final intervention session. Conclusions considering the effectiveness of the “unity-oriented psychology concepts instruction” on reducing depression and increasing spiritual well-being in bereaved mothers, this intervention can be used to alleviate the psychological pain in this group.