Brain alpha2-containing GABA-A receptors play a critical role in the modulation of anxiety- and fear-like behavior. However, it is unknown whether these receptors also play a role in modulating resilience to chronic stress, and in which brain areas and cell types such an effect would be mediated. We evaluated the role of alpha2-containing GABA-A receptors following chronic social defeat stress using mice deficient in the alpha2 subunit globally or conditionally in dopamine D1- or D2-receptor expressing neurons, e.g., within the nucleus accumbens (NAc). In addition, we examined the effect of lack of the alpha2-subunit on intermediates of the glutathione synthesis pathway. We found that alpha2-containing GABA-A receptors on D2-receptor positive but not on D1-receptor positive neurons promote resiliency to chronic social defeat stress, as reflected in social interaction tests. The pro-resiliency effects of alpha2-containing GABA-A receptors on D2-receptor positive neurons do not appear to be directly related to alterations in anxiety-like behavior, as reflected in the light-dark box and novel open field tests. Increases in indices of oxidative stress—reflected by increases in cystathionine levels and reductions in GSH/GSSG ratios—were found in the NAc and prefrontal cortex but not in the hippocampus of mice lacking alpha2-containing GABA-A receptors. We conclude that alpha2-containing GABA-A receptors within specific brain areas and cell populations promote stress resiliency independently of direct effects on anxiety-like behaviors. A potential mechanism contributing to this increased resiliency is the protection that alpha2-containing GABA-A receptors provide against oxidative stress in NAc and prefrontal cortex.