Abstract: Prostate cancer, the second most common cancer in men worldwide, causes a serious threat to human health.Notably, the androgen receptor (AR) plays a crucial role in the pathogenesis of prostate cancer, and the glucocorticoid receptor (GR) modulates downstream genes in certain AR signaling pathways.Thus, disrupting the AR and GR signaling pathways holds great promise for effective treatment of prostate cancer.This review provides a comprehensive overview of the structural characteristics and biological functions of AR and GR, and a systematic introduction to the recent breakthroughs in medicinal chemistry for prostate cancer treatment, including the development of novel androgen competitive AR antagonists, androgen non-competitive AR antagonists, AR degraders, GR antagonists and AR/GR dual antagonists, which offer novel insight for the treatment of castration-resistant prostate cancer.