Background: This study aimed to conduct a prospective, randomized, controlled clinical trial using, Qidan Tangshen Granule, a traditional Chinese medicine (TCM), as an antioxidant, to treat diabetic kidney disease (DKD) patients. Methods: A total of 355 patients were enrolled, and after exclusions, 219 patients were divided into an intervention group (n = 109) receiving Qidan Tangshen Granule treatment and a control group (n = 110) receiving conventional treatment. Demographic and physiological parameters were evaluated at baseline and 3 months and 12 months of follow-up. The levels of serum oxidants including 8-hydroxy-2 '-deoxyguanosine (8-OHdG) and 3-nitrotyrosine (3-NT), and the enzymic anti-oxidant, superoxide dismutase (SOD), were evaluated using enzyme-linked immunosorbent assays. Results: Qidan Tangshen Granule treatment significantly reduced hemoglobin A1c (HbA1c) and albumin-tocreatinine ratio (UACR) levels, improved renal function, and exerted antioxidative effects in DKD patients. Compared to the control group, the intervention group showed increased levels of SOD and decreased levels of 8OHdG and 3-NT, indicating reduced oxidative stress. Furthermore, the intervention group demonstrated a significant decrease in HbA1c and UACR levels and an improvement in glomerular filtration rate compared to the control group. Conclusions: Qidan Tangshen Granule may be a potential therapeutic option for the treatment of DKD, offering improved clinical outcomes for patients.