Background <p>This study analyzed the clinical data of 25 patients with refractory idiopathic membranous nephropathy (RIMN) treated with obinutuzumab, aiming to investigate its efficacy and safety.</p> Methods <p>A retrospective study was conducted on patients with RIMN who were treated with obinutuzumab, admitted to the Department of Nephrology at Qilu Hospital of Shandong University and the Affiliated Hospital of Jining Medical College from March 2022 to November 2023. The treatment of obinutuzumab was determined based on the individual patient’s specific circumstances. We collected clinical data including urinary protein-to-creatinine ratio (UPCR), serum albumin, creatinine, estimated glomerular filtration rate (eGFR) and circulating anti-phospholipase 2 receptor (PLA2R) antibodies for a minimum of 12&#xa0;months. The clinical efficacy and safety of obinutuzumab were evaluated in these patients.</p> Results <p>Among the 25 patients, 19 (76.0%, responders) achieved partial (<i>n</i> = 16) or complete (<i>n</i> = 3) response with obinutuzumab treatment. The median time to achieve partial response was 3.5&#xa0;months [interquartile range (IQR) 3.0–12.0&#xa0;months], and 6 patients were unresponsive to the treatment. After treatment with obinutuzumab, 19 of the 21 patients (90.5%) with positive phospholipase 2 receptor (PLA2R) antibodies achieved complete immunological remission (anti-PLA2R antibodies level &lt; 2 RU/mL). The median time to negativity was 6.0&#xa0;months (IQR 3.0–9.0&#xa0;months). The two patients who remained positive had PLA2R antibodies titers that decreased below 14 RU/mL and both achieved clinical remission. The renal function remained stable during the follow-up period. No relapse was observed. No severe adverse events related to obinutuzumab were observed.</p> Conclusion <p>Obinutuzumab could effectively relieve proteinuria, stabilize renal function and maintain good safety in patients with RIMN.</p>