Dementia cases are on the rise among our aging global population, and thus there is increasing urgency to identify efficacious interventions for preserving or ameliorating cognitive decline. Physical exercise, cognitive training and combined physical and cognitive interventions have been found to slow the decline of cognitive abilities in those with mild cognitive impairment (MCI), but the biological mechanisms underlying these changes need further clarification. This quasi-experimental within-subjects design compared changes in biomarkers during two-week exposures to physical exercise, cognitive intervention and the interactive physical and cognitive exercise system (iPACES™) as well as a 10-week iPACES intervention. Participants were evaluated over eight weeks at two-week intervals. Salivary bomarker levels of Cortisol, IGF-1 and DHEAS were assessed at each evaluation through saliva (passive drool collection). Each saliva sample was analyzed using enzyme-linked immunosorbent assays (ELISAs). Additionally, each sample was analyzed using bicinchoninic acid (BCA) protein assay to normalize protein concentration. Cognitive outcomes were also assessed, focusing on executive function via Stroop, Trails, and Flanker tests. This pilot study enrolled 14 older adults, 13 of which met criteria for MCI (MoCA<26), with ten participants completing the acute windows, seven completing the study and four compliant study completers. Results revealed significant cognitive improvements from baseline through all active components (e.g., pedaler, game, and iPACES™), but not during placebo. Results also revealed biomarker change during some active components. Furthermore, the changes for cognition were moderately correlated with biomarker changes, suggesting a link between neurobiological mechanisms and cognitive outcomes. Further research is needed to replicate and extend this pilot research; in particular, it would be useful to compare such interventions in a randomized controlled trial.