The associations between hypoglycemic medications, cordycepin, COVID-19 vaccination, and clinical outcomes of SARS-CoV-2 infection were examined in a retrospective cohort of patients with diabetic kidney disease (DKD) in Ningbo, China, between December 2022 and June 2023. Acute COVID-19 outcomes included fever, pneumonia, hospitalization, and prolonged symptoms. Short-term DKD outcomes at three months post-infection included a serum creatinine increase ≥ 30%, an estimated glomerular filtration rate (eGFR) decrease ≥ 10 mL/min/1.73 m2, a urinary albumin-to-creatinine ratio (UACR) increase ≥ 30%, a fasting blood glucose increase ≥ 1.1 mmol/L, and a hemoglobin A1c (HbA1c) increase ≥ 0.3%. Among 642 DKD patients with COVID-19, 66.8% were treated with sodium-glucose cotransporter-2 inhibitors (SGLT2i) at baseline, 36.9% with dipeptidyl peptidase-4 inhibitors (DPP4i), 30.8% with metformin, and 36.4% with cordycepin. Logistic regression analysis indicated that SGLT2i use was associated with a reduced risk of hospitalization and less worsening of UACR. Metformin use was linked to a lower incidence of COVID-19 pneumonia but an increased risk of serum creatinine elevation. DPP4i use showed no significant association with adverse outcomes. Cordycepin use was associated with reduced risks of hospitalization and serum creatinine elevation. Compared with unvaccinated patients, multiple-dose COVID-19 vaccination was associated with reduced risks of adverse outcomes, including prolonged COVID-19 symptoms, pneumonia, decreased eGFR, and elevated blood glucose and HbA1c levels. In conclusion, pretreatment with SGLT2i, cordycepin, and multiple-dose COVID-19 vaccination was associated with reduced adverse outcomes among DKD patients with COVID-19.