Diabetic kidney disease (DKD), is one of the most common vascular diseases caused by diabetes, eventually progressing into glomerular sclerosis. Qidantang Granule is a traditional Chinese medicine that is commonly used for DKD. However, there is still no experimental evidence for its effectiveness on DKD. 8-week-old Sprague Dawley male rats were fed on high-fat and high-sugar diet for 4 weeks, and then intraperitoneally injected with 35 mg/kg streptozotocin (STZ) to induce diabetes. Diabetic rats were randomly divided into three groups, and orally administrated with vehicle, 50 mg/kg or 200 mg/kg Qidantang Granule respectively, once daily for 9 weeks. Qidantang Granule effectively reduced food and water intake, body weight and fasting blood glucose, decreased inflammation and oxidative stress, ameliorated renal injury through suppressing PI3K signaling pathway in STZ-induced DKD rats. Our results provide experimental evidence to demonstrate the pharmacological mechanism of Qidantang Granule in the treatment of DKD.