Social isolation, when owners are not home, is a major stressor for dogs leading to separation anxiety and related behavioral and physiological issues. We investigate whether a digital interactive game requiring no human interference reduces stress response in dogs when isolated. An interactive game was developed specifically for canines. Dogs were domestically tested, totaling 15 days with and 15 days without the game. Twice-daily saliva samples were analyzed for cortisol stress hormone concentrations; ethograms were constructed. Combined data confirm that digital interactive games can lessen physiological and behavioral stress responses in dogs, and that the effect is modulated by a dog’s personality.