Background <p>Sadness can be a harbinger of serious medical conditions and a primary manifestation of depressive symptoms. Music is a promising modality for regulating sadness, although its effect on participants, whether with or without long-term depressive symptoms, remains unknown. In this study, the effect of music on sadness regulation was investigated using psychological and physiological indicators between depressed and non-depressed individuals.</p> Methods <p>Data were collected from 149 participants (18 to 29 years old). The participants were divided into two groups (depressed and non-depressed groups) based on their depressive symptoms, experienced sadness induction, and music intervention. Electrocardiogram signals were collected to measure heart rate variability (HRV).</p> Results <p>(1) Music alleviated sadness (increasing positive emotions, valence and dominance, while decreasing arousal); (2) sadness increased the duration between consecutive heartbeats, and music decreased this duration; (3) participants with depressive symptoms showed lower HRV than those without, and music enhanced HRV for the depressed group; (4) no significant difference in the effects of music was found between the two groups; and (5) the regulatory impact of music on sadness was not influenced by prior music listening habits.</p> Conclusions <p>The findings indicate that listening to music can be beneficial for both healthy and subclinical individuals when managing sadness. The findings underscore the importance of recognizing the role of music in promoting emotional well-being.</p> Trial registration <p>This trial was retrospectively registered on ClinicalTrials.gov PRS (Protocol Registration and Results System) (number NCT06516666) on July 22, 2024 (<a href="https://register.clinicaltrials.gov/">https://register.clinicaltrials.gov/</a>).</p>