The symptoms of anxiety and depression, accompanied with low self-esteem, are increasing in Taiwanese undergraduates. It is essential for the school to assist them in reaching mental health. Hence, the purpose of this study was to examine the effects of music therapy on anxiety, depression and self-esteem of undergraduates. Twenty-four I-Shou University undergraduates who showed greater anxiety and depression with lower self-esteem were randomly assigned to experimental and control groups. The experimental group was provided 20 hours of music therapy, whereas the control group did not receive any treatment. Both quantitative and qualitative analyses were utilized to evaluate the changes of the participants. The findings indicated that the experimental group demonstrated a reduction in anxiety immediately after the music therapy and after a two-month follow-up, but only reduced depression after the follow-up. Moreover, the experimental group expressed that they experienced more positive changes, including more pleasure, relaxation, and confidence, and fewer negative emotions.