This study aimed to investigate the efficacy of a combined adaptive cognitive training and structural-systemic family therapy protocol in reducing depressive symptoms and improving cognitive flexibility and inhibitory control. In a quasi-experimental design with pre-test, post-test, and two-month follow-up assessments and a control group, 32 adults (16 per group) diagnosed with mild-to-moderate depression were randomly assigned to either the experimental or control condition from three reputable family therapy clinics in Tehran. The experimental group received 12 sessions of standard structural-systemic family therapy plus 12 sessions of adaptive cognitive training focused on task-switching, set-shifting, response inhibition, and Stroop exercises; the control group received family therapy alone. Measures included the Beck Depression Inventory-II, Cognitive Flexibility Inventory, and computerized Stroop Color-Word Test. Repeated-measures multivariate analysis of variance revealed that the combined intervention produced highly significant reductions in depressive symptoms and substantial improvements in cognitive flexibility and inhibitory control at post-test and two-month follow-up (p < .001), with very large effect sizes (η² ranging from 0.586 to 0.923). Improvement in inhibitory control remained fully stable at follow-up. Adding adaptive cognitive training to structural-systemic family therapy constitutes a highly effective, clinically meaningful third-generation combined protocol for treating mild-to-moderate depression that not only alleviates emotional symptoms but also directly remediates persistent cognitive deficits, thereby enhancing relapse-prevention potential. This approach is particularly recommended for collectivist cultures and systemic treatment contexts.