It is necessary to determine which antihypertensive drug is better, diphenhydramine or sartan, according to the patient’s specific situation. Diphenhydramine is used to lower blood pressure by expanding blood vessels and reducing vascular resistance. The main adverse effects include headache and edema. Sartans lower blood pressure by inhibiting angiotensin II receptors, and are recommended for patients with hypertension combined with renal insufficiency because they have little effect on renal function. In patients with hypertension combined with coronary artery disease or heart failure, sartans are recommended because of their positive effect on reversing myocardial remodeling as observed from long-term treatment. Patients with moderate to severe hypertension require a combination of two or more antihypertensive drugs, and sartans and diphenes are often used in combination, such as valsartan amlodipine tablets. Both diphenhydramine and sartans are first-line antihypertensive drugs and should be selected individually according to the patient’s condition.