Chronic stress promotes life-long risk for neuropsychiatric decline by increasing neuroinflammation and disrupting synaptic health and plasticity. Our lab and others have demonstrated that non-invasive gamma sensory stimulation (flicker) modulates immune signaling, restores microglial function, and improves cognitive performance in male mouse models of Alzheimer’s disease. However, no research to date has studied the effects of flicker in the context of stress. Accordingly, our goal for this study was to determine if flicker mitigates neuropsychiatric-like behavioral deficits and rescues glial and synaptic pathology following chronic stress. Daily audiovisual flicker intervention was introduced concomitantly with daily stress exposure (28 days) at multiple frequencies (10-40Hz or no stimulation control) in male and female C57BL6 mice (n=6/group/sex). The mice were then tested for a range of neuropsychiatry-related behavioral tests. We quantified transcriptomic changes in cortical pyramidal neurons, microglia, and astrocytes to identify cell-type specific genes modulated by flicker intervention in chronically stressed mice. To determine how flicker mitigates stress-induced changes to glia and synaptic spines, we quantified spine density changes in Thy1-GFP mice. We measured glial morphology as an additional assay of microglial and astrocyte reactivity in the medial prefrontal cortex, a region highly sensitive to psychological stress. Our findings indicate that audiovisual flicker protects against stress-induced behavioral deficits and mitigates stress-induced neuroimmune responses in a sex- and frequency-specific manner. Together, our findings show that frequency optimized flicker improves stress pathology at molecular, cellular, and behavioral levels. Thus, flicker may prevent neuropsychiatric health decline in conditions with sex dimorphic symptoms and prevalence.