Objectives: Glucocorticoid (GC)-induced Adverse Reactions (ARs) have been extensively studied due to their potential impact on patients' health. Adding to the existing literature, this study aimed to establish the potential correlation between two polymorphisms [Adenosine Triphosphate-Binding Cassette B1 (ABCB1) C3435T and Plasminogen Activator Inhibitor-1 (PAI-1) 4G/5G] and various GC-induced ARs in Nephrotic Syndrome (NS) patients. Methods: Herein, 513 NS patients who underwent GC treatment at the First Affiliated Hospital of Zhengzhou University were enrolled. Following that, ABCB1 C3435T and PAI-1 4G/5G genotyping was performed and compared across groups. Subsequently, multivariate analyses were performed on clinical data to determine the association between the ABCB1 C3435T and PAI-1 4G/5G polymorphisms and GC-induced ARs. Results: We identified ABCB1 C3435T as an independent risk factor for the development of Steroid-Associated Avascular Necrosis of the Femoral Head (SANFH) (OR:2.191, 95%CI:1.258-3.813, p=0.006), but not as a risk factor for Steroid Diabetes (S-DM) occurrence. On the other hand, PAI-1 4G/5G was identified as an independent risk factor for the development of both SANFH (OR: 2.198, 95%CI: 1.267-3.812, p=0.005) and S-DM (OR: 2.080, 95%CI: 1.166-3.711, p=0.013). Notably, no significant correlation was found between the two gene polymorphisms and other GC-induced ARs. Conclusions: Assessing ABCB1 C3435T and PAI-1 4G/5G before steroid treatment in NS patients could be useful in evaluating patients at a high risk of developing SANFH and S-DM.