Objective To simulate modern social stress using a pre-pregnancy chronic mild stress (CMS) model and to explore the mechanisms of emotional, behavioral, and neurodevelopmental changes in male offspring of pre-pregnancy liver qi stagnation female mice through corticosterone (CORT)-brain-derived neurotrophic factor (BDNF) extracellular signal-regulated kinase (ERK) 1/2 signaling cascade-mediated hippocampal injury. This study aimed to elucidate the impact of negative life events on offspring and the interventional mechanism of Shuyu Capsules. Methods CMS stress was used to induce pre-pregnancy depression in female rats (liver qi stagnation state), followed by intervention with Shuyu and fluoxetine capsules. After screening, male rats were mated and 12 male offspring from each group were selected for behavioral testing and detection of serum CORT levels by enzyme-linked immunosorbent assay. BDNF, ERK1/2, phospho (p)-ERK1/2, cAMP-response element binding protein (CREB), and p-CREB protein levels in the hippocampus were detected by Western Blot, and BDNF, ERK1, ERK2, and CREB mRNA levels in the hippocampus were detected by reverse transcription-polymerase chain reaction(RT-PCR), to verify the effects of pre-pregnancy CMS on the BDNF-ERK1/2-CREB signaling pathway and to investigate the key micro-mechanisms of Shuyu Capsules on emotional and learning memory-related behaviors of male offspring of females with pre-pregnancy liver qi stagnation syndrome. Results The distance, number of entries, and duration of stay in the central area in open-field experiments were significantly reduced in offspring in the model group (all P<0.05). The escape latency during the exploration period of the water-maze experiment was significantly prolonged (P<0.05) and the swimming distance, duration of the target quadrant, and number of platform crossings were significantly reduced (P<0.05, P<0.05, P<0.01), the suspension time and frequency in the forced-swimming experiment were increased (P<0.05, P<0.01), and the incubation period was shortened (P<0.05) in offspring in the model group. Prophylactic treatment with Shuyu Capsules and fluoxetine improved the depression-like behavior and cognitive impairment in the offspring in the model group. Biochemical tests showed that CORT levels were increased in the CMS model group (P<0.05), BDNF, p-ERK1/2, and p-CREB protein levels in the hippocampus were decreased (all P<0.05), and BDNF, ERK1, ERK2, and CREB mRNA levels were significantly reduced (P<0.01, P<0.05, P<0.01, P<0.05). Treatment with Shuyu Capsules and fluoxetine increased the CORT content and BDNF, ERK1/2, and CREB protein and mRNA levels in male offspring to varying degrees. Conclusions High levels of CORT in offspring act selectively on the hippocampus, exerting adverse effects on the emotional and learning memory functions of rats by downregulating the BDNF-ERK1/2 signaling cascade. The Chinese medicine Shuyu Capsules can reduce the impact of an adverse intrauterine environment on offspring development by correcting abnormal levels and pathways of glucocorticoids.