Objective To explore the effects of music therapy combined with primary medical gymnastics on motor function， emotional state， dopamine， 5-hydroxytryptamine（ 5-HT）， and norepinephrine （NE） in patients with first-time stroke and depressive disorder. Methods A total of 130 patients with firsttime stroke and depressive disorder admitted to the Department of Rehabilitation of Nanfang Hospital， Southern Medical University from January 2021 to December 2023 were selected as study subjects. Patients were assigned using a random number table method to either the control group（ n=65， conventional treatment） or the observation group（ n=65， music therapy combined with primary medical gymnastics on the basis of the control group）. After four weeks of treatment， the efficacy， motor function［ Fugl-Meyer Assessment （FMA）， Modified Barthel Index（ MBI） scores］， emotional state［ Hamilton Depression Scale-17（ HAMD- 17）， Self-Rating Anxiety Scale（ SAS）， and Self-Rating Depression Scale（ SDS） scores］， and neurotransmitter levels were compared between the two groups. Results The total effective rate of observation group patients was 89.23%（ 58/65）， which was higher than the 75.38%（ 49/65） of control group patients， and the difference was statistically significant（ χ2=4.279，P=0.039）. Observation group patients showed FMA scores［ （40.36±5.81） vs.（ 35.89±6.33）］， MBI scores［ （28.48±8.01） vs.（ 21.33±6.42）］， HAMD-17 scores ［（22.32±1.52） vs.（ 19.39±1.50）］， SDS scores［ （11.51±1.60） vs.（ 7.19±1.46）］， SAS scores［ （8.88± 1.92） vs.（ 7.55±1.83）］， dopamine［ （79.16±18.43） μg/L vs.（ 49.46±16.30） μg/L］， 5-HT level ［（75.14±23.81） μg/L vs.（ 64.91±20.16） μg/L］， and NE level difference before and after treatment ［（25.86±4.07） ng/L vs.（ 22.38±4.46） ng/L］ were significantly higher than those in control group（ t=4.194， 5.616， 11.062， 16.080， 4.043， 9.732， 2.644， 4.648； all P＜ 0.05）. Conclusions The combination of music therapy and primary medical gymnastics can effectively enhance the motor function of first-time stroke patients with depressive disorder， while also helping to improve their emotional state and dopamine， 5-HT， NE levels.