Abstract Aim and objective To investigate the effectiveness of music interventions on physiological and psychological stress response in intensive care unit (ICU) patients. Background ICU patients are exposed to several physiological and psychological stressors during their treatments. Music interventions can be implemented to control these negative effects. Design Systematic review and meta‐analysis conducted according to PRISMA Guidelines. Method Seven electronic literature databases, reference lists of similar reviews, grey literature and the Clinical Trials Registry were searched for potential studies up to 30 January 2022. Studies were expected to meet PICOS inclusion criteria. Two reviewers independently assessed the risk of bias of the included studies by using the Cochrane Collaboration tool. Overall, meta‐analysis and subgroup analyses (comparator group and music session frequency) were performed using RevMan 5.4. Meta‐analysis was conducted when data were available; otherwise, a narrative description was provided. Results Twenty‐five articles were included in this meta‐analysis. Across all studies, regardless of the comparator, music was found to significantly reduce anxiety scores with an SMD of 1.81 ([95% CI: −3.09,‐0.53]; p = .006). Music was found to significantly reduce anxiety scores with an SMD of 1.97 (95% CI: −3.66, −0.28) compared to standard care (p = .02), but there was no significant change in anxiety scores in comparison with the noise cancellation group (p > 0.05). It was found that multiple music sessions reduced the anxiety level better than a single music session. Music had no effect the systolic/diastolic blood pressure, respiratory or heart rate level in both subgroup and general analyzes concerning the physiological stress (p > 0.05). Conclusions Music interventions involving multiple sessions can be used as a nursing intervention to control the anxiety levels of ICU patients. Relevance to the clinical practice Using music to reduce anxiety and stress levels may reduce the pharmacological need (for sedative or antipsychotic medications) and the risk of associated side effects in ICU patients.