Objective <p>The study is proposed to uncover the protective effect of Banxia Xiexin Decoction (BXD) on polycystic ovarian syndrome (PCOS).</p> Methods <p>PCOS in rats was induced by continuous injection of DHEA. BXD was continuously administered, and the pathological changes of the ovarian tissue were observed by HE staining. Cleaved caspase-3, TLR4, and IL-6 were measured by immunohistochemical staining, RT-qPCR, and immunoblotting. The regulatory effects of BXD on serum hormones in PCOS rats were evaluated by ELISA. Granulosa cells (GC) were isolated from ovarian tissues of PCOS rats, and cell viability, apoptosis, and cell cycle progression were evaluated, and Cleaved Caspase-3 and IL-6 expressions were determined.</p> Results <p>BXD effectively improved the damage of ovarian tissue, restored abnormal hormone levels, and inhibited cell proliferation and inflammatory response in PCOS rats. BXD blocked the TLR4/IL-6 axis by up-regulating miR-20b-5p.</p> Conclusion <p>BXD negatively regulates the TLR4/IL-6 axis by up-regulating miR-20b-5p, inhibiting the proliferation and inflammatory response of GC in PCOS.</p>