Objective To compare the efficacy and safety of Shuangbai tablets and irbesartan in the treatment of proteinuria. Methods A retrospective analysis was conducted on patients with chronic glomerulonephritis who visited the outpatient department of Ruijin Hospital from January 2016 to February 2018. All the patients received irbesartan or Shuangbai tablets as monotherapy and were classified with syndrome differentiation of traditional Chinese medicine(TCM). Their clinical information, blood pressure and laboratory test were performed at 0, 4, 8, 12, and 24 weeks. Results One-hundred and nineteen patients were enrolled in the study, in which 54 cases were in the irbesartan group and 65 cases were in the Shuangbai tablet group. In all patients, the main TCM types were “pifeixiqu” type (56.3%), “pishenyangxu” type (20.2%), and “qiyinliangxu” type (21.8%). The 24-hour urinary protein of baseline level in the irbesartan group was 704 (448，1 090) mg/d, and it was significantly decreased to 456 (300,660), 428 (288,793), 510 (327,949), and 446 (273,801) mg/d at 4, 8, 12, and 24 weeks, respectively. The 24-hour urine protein level of baseline in the Shuangbai tablet group was 571 (390,1 049) mg/d, and it was significantly decreased to 491 (200，861), 432 (252，925), 478 (267，858) mg/d and 420 (175，742) mg/d at 4, 8, 12, and 24 weeks, respectively. There was no significant difference in proteinuria between the two groups. There was no statistical difference in the therapeutic effect among patients with different TCM syndrome types. The symptoms of lower back pain (59.3% vs 13.8%, P<0.001) and dry mouth and throat (24.1% vs 6.2%, P=0.005) in the Shuangbai tablet treatment group were significantly improved compared to those in the irbesartan group. The blood pressure of patients in the irbesartan treatment group decreased significantly at 12 and 24 weeks compared to it at enrollment. There were no significant adverse reactions in the Shuangbai tablet treatment group. Conclusions Shuangbai tablets can effectively reduce the urine protein level in chronic glomerulonephritis patients. It can also significantly improve the symptoms of lower back pain, dry mouth and throat in patients. Shuangbai tablet treatment showed a lower incidence of adverse reactions and can be used as an alternative medicine for patients with normal blood pressure, angiotensin-converting enzyme inhibitor(ACEI)/angiotensin receptor blocker(ARB) intolerance, or chronic glomerulonephritis without renal biopsy.