This study examined oxytocin expression in experimental models of Alzheimer’s disease (AD), and evaluated the therapeutic potential of treatment with oxytocin. They investigated changes in oxytocin expression in APP/PS1 mouse model and developed a chronic intranasal treatment protocol to increase oxytocin levels in the brain. Then, tested oxytocin as a potential approach to attenuate microglial activation and reverse memory deficits. This dataset includes source data used to assemble different figures in the publication. The source data contains data about hypothalamic expression of oxytocin is reduced in AD models, chronic intranasal administration of oxytocin increases hippocampal oxytocin and attenuates fear response in mice, cellular and molecular impact of intranasal oxytocin in APP/PS1 mouse brains, oxytocin attenuates AβO-induced microglial activation in vitro, and intranasal oxytocin reverses social and non-social memory deficits in aged APP/PS1 mice.