Background: Major depressive disorder (MDD) is associated with emotional, motivational, cognitive, behavioral, and biological symptoms. Depressed people have negative emotional experiences and are usually unhappy, frustrated, distressed, impatient, and discouraged. Objective: This study aimed to determine the effectiveness of emotion-focused therapy on emotional, cognitive, motivational, and biological symptoms of major depressive disorder. Method: The present study was a quasi-experimental research with pretest, posttest, and follow-up design. The statistical population of the study consisted of all clients referred to the beautiful mind counseling center in Bojnourd in 2019-20, among which 30 people were selected using purposeful sampling method and were assigned to two experimental (n=15) and control (n=15) groups. Data were obtained from a researcher-made depression questionnaire. Data were analyzed using repeated measure analysis of variance and SPSS software (version 24). Results: The results indicated that emotion-focused couple therapy was effective in reducing emotional symptoms (P<0. 01), cognitive (P<0. 01), motivational (P<0. 01), and biological symptoms (P<0. 01) of major depressive disorder. Conclusion: It can be concluded that emotion-focused couple therapy is effective in reducing emotional, cognitive, motivational, and biological symptoms of people with major depressive disorder and this treatment can be used to improve the problems of depressed individuals.