Yiqi Yangyin complex (YYC), the homology of medicine and food, is comprised of Polygonati Rhizoma, Lycii Fructus, Codonopsis Pilosula, and Rehmanniae Radix. Herein, the YYC polysaccharide treatment effectively attenuated the progression of MGH in a mice MGH model-induced with estrogen and progestogen. YYC significantly relived hormonal disorders by reducing the levels of estrogen receptor α (ERα) and progesterone receptor (PR), and substantially elevated the protein level of BCL2-associated X (Bax) and significantly down-regulated expression of B-cell lymphoma-2 (BCL-2). Finally, the key targets of ERα, PR, Bax and BCL-2 were predicted and significantly enriched on estrogen signaling pathway and apoptosis pathway by network pharmacology. This finding suggests that YYC may influence the sex hormones level through estrogen signaling pathway and then induce apoptosis to balance normal functions of mammary gland. This study thus provided evidences for the potential therapeutic efficacy of YYC on MGH and revealed the correlated regulatory signaling pathways.