The use of existing public spaces by people living with dementia, such as museums and art galleries, are becoming popular due to their ability to facilitate programs which promote social engagement and inclusion. However, few studies have investigated physiological outcomes of art gallery-based programs. Using a quasi-experimental design, the present study aimed to investigate the levels of salivary biomarkers of cortisol and interleukin-6, quality of life (QoL), depressive symptoms, cognition, and wellbeing, after attending the National Gallery of Australia (NGA) Art and Dementia program. Twenty-eight people living with dementia, each supported by a carer or family member, were recruited for a six-week program and were followed up at twelve weeks. In total, 25 participants (17 female; mean age 84.6±7.27 years) completed the study, and 22 provided viable saliva samples. The waking to evening salivary cortisol ratio was higher post-intervention (p = 0.033), and returned to baseline levels at follow-up (p = 1.00), indicating a more dynamic salivary cortisol rhythm in response to the six-week program. Interleukin-6 levels remained unchanged (p = 0.664). No improvements in QoL (DEMQOL-Carer) were observed between baseline and post-intervention (p = 0.076). However, self-reported depressive symptoms decreased post-intervention compared with baseline (p = 0.015), and memory (immediate recall) (p = 0.009) and verbal fluency (p = 0.027) improved between the same timepoints. The NGA Art and Dementia program appears to have quantifiable benefits, including improved hypothalamic-pituitary-adrenal axis function, justifying a need for longer controlled trial inclusive of physiological outcomes.