Introduction: Hemodialysis patients may experience various problems, such as physical and psychological complications. The most frequently occurring psychological complication is stress. Stress in patients with hemodialysis can increase the cortisol level in the blood. Therefore, this study is aimed at analyzing the effects of classical music therapy and breathing exercises on the stress level and the cortisol level in the hemodialysis patients. Methods: This true experiment study was conducted using pretest-posttest control group design. The samples involved patients with hemodialysis totaling 40 respondents comprising of 20 people in the control group and 20 people in the treatment group chosen by using random allocation sampling method. The treatment group was given an intervention of combining classical music therapy and breathing exercises done twice a week for 30 minutes according to the respondents’ hemodialysis schedule. On the other hand, the control group received the standard intervention. While the stress level was measured using PSS (Perceived Stress Scale), the measurement of the cortisol level was done through laboratory examination using ELISA method (Enzym Linked Immunosorbent Assay). Moreover, the data were analyzed using independent t-test and Ancova test with the significance level of p < 0.05. Results: There were differences in the stress level (p=0.000) and the cortisol level (p=0.000) between the two groups. Conclusion: Based on the results, this study concludes that the combination of classical music therapy and breathing exercises is an innovative intervention which can decrease the stress level and the cortisol level in the hemodialysis patients.