INTRODUCTION: Stroke not only leads to physical dysfunction in people living with stroke, but also causes emotional and cognitive abnormalities, which significantly affect survival and quality of life. Prior research has shown that music-supported therapy (MST) has the ability to improve depression and cognitive performance through stimulation of the central nervous system. Nevertheless, there is a dearth of rigorous systematic assessments of the effectiveness of MST in improving depression and cognitive impairments in people living with stroke, as well as the impact of these benefits on their overall quality of life. This systematic review and meta-analysis aimed to assess the impact of MST on emotional and cognitive impairments in people living with stroke, as well as its influence on their quality of life. METHODS: The PRISMA 2020 guidelines were followed to search for articles on MST treating depression and cognitive issues in people living with stroke in the PubMed, Embase, Web of Science, Wanfang, CNKI, CSTJ, and SinoMed databases, with a cut-off date of July 11, 2024. Two researchers utilized the revised Cochrane RoB-I risk of bias technique to evaluate the quality of all relevant literature obtained. They subsequently extracted and meta-analyzed the data using Review Manager 5.4.1 software. RESULTS: Seventy-two studies involving a total of 5,543 people living with stroke were included, and the meta-analysis revealed that MST had a significant effect on depression and cognitive deficits in people living with stroke (SMDHAMD = 1.49, 95% CI: 1.21-1.76, p <
0.001, MDMMSE = 2.53, CI: 1.60-3.45, p <
0.001, MDMoCA = 3.59, CI: 2.57-4.62, p <
0.001), which took effect from 2 weeks of treatment and was accompanied by an increase in serum 5-HT level (SMD5-HT = 2.22, CI: 1.47-2.96, p <
0.001) and improvements in depression and cognitive function, daily living abilities (SMDADL = 1.72, CI: 1.32-2.11, p <
0.001), limb motor function (SMDFMA = 1.25, CI: 0.47-2.02, p <
0.001), and neurological function (SMDNIHSS = -1.77, CI: -2.50 to -1.04, p <
0.001). CONCLUSION: MST effectively improves depression and cognitive function of people living with a stroke and enhances their ability to perform daily activities and limb motor function. Importantly, improvements in depression and cognitive function occur earlier than those in daily life ability and neurological function. Additionally, the level of serum 5-HT may serve as a potential indicator for assessing the effectiveness of MST.