Background: Patients with major depressive disorder experience many difficulties and need strategies to enhance adherence, cope with a chronic condition, and maintain a positive mental status which must address issues in training and patient education. Aim: The study aim was to examine the effectiveness of the psychoeducational program for self-management strategies to cope among patients with depression. Methods: A quasi-experimental design (one group pre/post-test) was used in the current study. It was carried out in the Outpatient Department at Psychiatric Hospital in Beni-Suef Governorate, Egypt. A purposive sample of sixty psychiatric patients medically diagnosed with the major depressive disorder was recruited in this study. Tools: consisted of four parts: Clinical and socio-demographic characteristics sheet, Self-rating depression scale (SDS), Self-management strategies, and The COPE inventory. Results: The findings of this study verified that statistically significant relation pre/post and pre/follow-up observations in self-rating depression scale, self-management strategies for people with depression, and the 15-scales of the coping inventory and statistically significant relation between post and follow-up observations in self-management strategies for people with depression and the 15 scales of the COPE inventory (p≤0.01 and p≤0.05). Conclusion: The results demonstrated that, the psycho-educational program is effective in promoting positive self-cope strategies for patients with depression. Recommendations: Nurses in psychiatric organizations, along with other healthcare members, should help patients develop, and use more self-management techniques and coping strategies.