BACKGROUND: Depression is a prevalent mental health disorder with significant impacts on individuals and families. We hypothesize that combining family cognitive therapy (FCT) with pharmacotherapy will be more effective in managing depression and improving family dynamics than pharmacotherapy alone. AIM: To investigate the effects of FCT combined with sertraline on depression, aggressive behavior, and family functioning in patients with major depressive disorder (MDD). METHODS: This study involved 178 patients diagnosed with MDD at the Shaoxing 7th People's Hospital from January 2022 to April 2024. Patients were divided into two groups according to whether they received FCT. FCT included both patient-focused cognitive therapy and family-focused psychological guidance over a 12-week period. RESULTS: The observation group receiving combined treatment showed significantly greater reductions in depressive symptoms (Beck Depression Inventory scores: 27.4 ± 4.7 to 18.6 ± 5.2) compared to the control group (28.1 ± 5.5 to 20.9 ± 4.9), with CONCLUSION: The combination of FCT with sertraline effectively reduces depressive symptoms and improves family dynamics in patients with MDD.