Background <p>Evidence on the impact of music-making interventions on brain plasticity in older adults is limited.</p> Aims <p>To investigate whether music-making interventions in older adults induce neurobiological changes and if such changes relate to cognitive improvements.</p> Methods <p>A systematic search was conducted in Medline, PsycINFO, and Scopus. Inclusion criteria targeted randomised controlled trials with older adults (with and without mild cognitive impairment [MCI]), music-making interventions as exposure, and neurobiological measures as the primary outcome.</p> Results <p>Six studies (555 cognitively intact older adults) met inclusion criteria—five used piano training, one used choral singing. Three studies had overlapping cohorts, and four had a high risk of bias. One study employed electroencephalography (EEG) to measure frontal and parietal activity, while five used structural MRI to assess cortical, subcortical, and white matter integrity. Methodological heterogeneity limited comparability. Findings in the piano group included increased frontal theta power during an improvisation task, greater grey matter volume in the dorsolateral prefrontal cortex and cerebellum, slower fibre density decline in the fornix and preserved grey matter volume in the right auditory cortex and hippocampus. Only one study reported a positive correlation between neurobiological changes and executive functioning improvements. No studies assessed neurobiological outcomes in MCI.</p> Discussion <p>Evidence on music-making interventions and neuroplasticity in older adults remains inconclusive due to limited studies, high risk of bias, and methodological variability. While preliminary findings suggest potential neurobiological changes with music-making interventions, there is insufficient evidence to draw firm conclusions.</p> Conclusions <p>High-quality trials are needed to clarify the neurobiological impact of music-making, particularly in MCI populations.</p>