Background: Glucocorticoids are essential for maintaining homeostasis and regulating physiological functions, including metabolism, cardiovascular health, and immune responses. They are commonly used in treatment for prostate cancer, but their mechanisms underlying castration-resistant prostate cancer (CRPC) remain unclear. Glucocorticoids can stimulate cell death and decrease inflammation, but their effects on prostate cancer cells remain unclear. Methods: Following PRISMA 2020 guidelines, this systematic review focused exclusively on full-text articles published in English between 2014 and 2024. To ensure the inclusion of high-quality sources, editorial pieces and review articles were excluded unless they were accompanied by a DOI. The literature search was conducted using several reputable databases, including ScienceDirect, PubMed, and SagePub, to comprehensively gather relevant studies. Result: The study conducted a comprehensive review of over 1,000 publications sourced from reputable databases, including ScienceDirect, SagePub, and PubMed. Following an initial screening, eight publications were identified as warranting more in-depth analysis. Consequently, a thorough review of these selected studies was performed to ensure a detailed and rigorous evaluation. Conclusion: Glucocorticoid receptors play a crucial role in the treatment of prostate cancer, affecting normal cell proliferation and accelerating tumor growth. Elevated expression of these receptors can induce drug insensitivity, leading to potential adverse effects. Clinical studies are needed to explore the feasibility of reducing GC use during chemotherapy and abiraterone treatment.