<p>This study aims to systematically evaluate the safety of rituximab (RTX) in pediatric nephrotic syndrome (NS) using real-world data from the US Food and Drug Administration Adverse Event Reporting System (FAERS). We analyzed FAERS data from Q1 2013 to Q4 2024, focusing on individual case safety reports (ICSRs) involving NS patients under 18 years old where RTX was the primary suspected drug. Adverse events (AEs) were coded using preferred terms (PTs) and mapped to system organ classes (SOCs). Four pharmacovigilance data analysis methods—reporting odds ratio (ROR), proportional reporting ratio (PRR), multinomial gamma Poisson shrinkage (MGPS), and Bayesian confidence propagation neural network (BCPNN)—were employed to assess drug-related AE risks. Among 275 RTX-related ICSRs, the most frequently reported AEs were hypogammaglobulinemia and granulocytopenia. The strongest signals were observed for CD19⁺ lymphocyte depletion, decreased blood immunoglobulin A (IgA), and decreased blood immunoglobulin G (IgG). The median time to AE onset was 7 days (IQR 0–148.5 days), with the majority of AEs (<i>n</i> = 74) occurring within the first month of RTX treatment. RTX use in pediatric NS is linked to significant immune and hematologic AEs, particularly within the first month of treatment. These findings support tailored monitoring strategies to mitigate risks while leveraging RTX’s therapeutic benefits.</p>