Major depressive disorder is one of the most common psychiatric disorders in the world. It is essential to study and use effective, available, and affordable psychotherapy methods along with drug therapy to manage the symptoms of this disease. Therefore, the current study aimed to determine the effect of mobile phone-based logotherapy on depression, suicidal ideation, and hopelessness in patients with major depressive disorder by using a mixed-methods approach. In the first phase of this mixed-methods study, 70 patients completed the quantitative phase (control group = 35, intervention group = 35). The intervention group received an 8-week mobile-based logotherapy program via WhatsApp (one 180-min module per week) combined with sertraline, while the control group received just sertraline plus education about pharmacotherapy. Data was collected before, immediately after the intervention, and 3 months later using the Beck depression inventory short form items (BDI-13), the Beck hopelessness scale (BHS), and the Beck scale for suicide ideation (BSSI). Then, a qualitative study on the intervention group was conducted to explain the findings of the quantitative phase. The repeated measure MANOVA revealed a significant interaction effect of time and group on the set of dependent variables (F(6,63) = 25.218, P < 0.001). Qualitative analysis confirmed the efficacy of sertraline plus mobile-based logotherapy on depression, suicidal ideation, and hopelessness in the intervention group. Three key themes extracted from the participants’ experiences of mobile-based logotherapy were “efficient instruction”, “user-friendly intervention” and “constructive change”. Mobile-based logotherapy through WhatsApp was an effective psychotherapy method for decreasing depression, hopelessness, and suicidal ideation in patients with major depressive disorder. It is suggested that educational, institutional, and technological infrastructure for providing and using mobile-based logotheapy for patients with major depressive disorder be considered in the mental health care system.

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