Objective To compare the relative efficacy and safety of dual blockade with sole blockade of the renin-angiotensin-aldosterone system in diabetic kidney disease. Method Studies were selected by searching the databases of MEDLINE, EMBASE, PubMed, and China National Knowledge Infrastructure (CNKI). All trials with angiotensin-converting enzyme inhibitor (ACEI) + angiotensin II type 1 (AT1) receptor blocker (ARB) (combination therapy), ACEI alone, or ARB alone (monotherapy) for treatment of diabetic kidney disease were included. The clinical parameters included for comparison were the progression to end-stage kidney disease (ESKD) or the outcomes of death, serum creatinine, glomerular filtration rate (GFR), serum potassium, 24-h urinary protein, urine albumin-to-creatinine ratio (UACR), urinary albumin excretion rate (UAER), and blood pressure. Results Twenty-two studies involving 6492 participants were eventually included. Compared to ACEI or ARB alone, a combination of ACEI and ARB can greatly reduce urine protein by 160 mg/d, the level of ACR significantly, as well as the systolic and diastolic blood pressures. The increase of serum creatinine and the decrease of GFR were more obvious in the combination treatment group. There was no significant difference in endpoint events between the two groups. The serum potassium level was significantly increased in the combination treatment group. Conclusions ACEI combined with ARB in the treatment of diabetic kidney disease can significantly reduce the level of proteinuria, decrease the blood pressure, and delay the progression of kidney disease. Moreover, it has some risk of increasing serum potassium and serum creatinine compared with monotherapy; so, careful attention is needed in dual blockade treatment.