Selective serotonin reuptake inhibitors (SSRIs) are the most popular antidepressant medications used to manage perinatal mood disturbances, yet our understanding of how they affect the microbiome‐gut‐brain axis of the mother and offspring is limited. The purpose of this study was to determine how peripartum SSRI treatment may prevent the effects of gestational stress on plasticity in the maternal hippocampus, plasticity in the neonatal brain and related changes in gut microbiota. To do this Sprague–Dawley female rats were left untreated or subjected to unpredictable stress during pregnancy. Half of the females were supplemented daily with fluoxetine. On postpartum day 2 brains were collected for measurement of plasticity (neurogenesis and microglia content) in the maternal hippocampus and in the neonatal brain. Glucocorticoid receptor density was also investigated in the maternal hippocampus. Microbiota composition was analyzed in fecal samples of dams during and after pregnancy, and colon tissue samples from offspring on postnatal day 2. Main findings show there are significant changes to the maternal microbiome‐gut‐brain axis that may be fundamental to mediating plasticity in the maternal hippocampus. In addition, there is significant impact of gestational stress on neonatal gut microbiota and brain microglia density, while the effects of SSRIs are limited. This is the first study to explore the impact of gestational stress and SSRIs on the microbiome‐gut‐brain axis in the mother and neonate. Findings from this study will help inform pathways to intervention strategies including stress reduction techniques and/or microbiota targeted nutritional approaches directed towards improving maternal gut health and outcomes for mother and neonate.