Generalized anxiety disorder (GAD), a common, debilitating condition, involves psychological and physiological dysfunction. Sandplay therapy (SPT), a multisensory treatment modality, has been successfully used to reduce anxiety ratings for individuals suffering from GAD using the Hamilton Anxiety Rating Scale (HAM-A) and the General Anxiety-7 (GAD-7). Because GAD involves sensory processing alterations in the thalamus, which may also be implicated in SPT, it would be beneficial to accompany evaluation with a physiological measurement targeting the thalamus. Using an A-B single-subject design, this case study explores whether clinical improvement in a GAD patient treated with SPT is associated with brain metabolite changes, specifically the N-acetylaspartate to creatine (NAA/Cr) ratio (a measure of neuronal viability) in both thalami using proton magnetic resonance spectroscopy. With no improvement during the waiting period, after 18 sessions of SPT, the participant (female, age 23) showed clinically significant improvement in symptoms of anxiety as measured by the HAM-A and GAD-7, and also showed improved NAA/Cr ratio to the healthy range in the right and left thalamus. The effectiveness of SPT in reducing symptoms of anxiety in this study is consistent with previous findings. The results also suggest an association between clinical improvement and metabolite changes in the thalamus and may underscore the multisensory aspects of SPT as an essential mechanism of change. Future studies regarding interpretation of the NAA/Cr ratio are recommended. Limitations are discussed.