Doxylamine vs Diphenhydramine: Which Sleep Aid Is Right for You?

When you can’t sleep, doxylamine, a sedating antihistamine used in over-the-counter sleep aids like Unisom SleepTabs and diphenhydramine, the active ingredient in Benadryl and many generic sleep medications are two of the most common choices. Both are antihistamines, but they work differently in your body—and that difference matters if you’re trying to get rest without grogginess, dry mouth, or next-day fog.

Do you need something that knocks you out fast and keeps you asleep? Doxylamine lasts longer—up to 8 hours—so it’s better for people who wake up in the middle of the night. Diphenhydramine kicks in quicker, usually within 20 to 30 minutes, but it often wears off sooner, which might leave you tossing and turning after 4 to 6 hours. If you’re using it for allergies during the day, diphenhydramine might be fine. But if you’re using it as a nightly sleep aid, doxylamine’s longer action can mean fewer awakenings and more deep sleep.

Side effects are where things get tricky. Both cause dry mouth, dizziness, and blurred vision, but diphenhydramine is more likely to cause next-day grogginess, especially in older adults. Studies show that people over 65 who take diphenhydramine regularly have a higher risk of confusion, falls, and even memory problems over time. Doxylamine isn’t risk-free, but it’s generally considered slightly gentler on cognition for short-term use. Neither should be used long-term without talking to a doctor—your body builds tolerance, and you might end up needing more just to fall asleep.

Here’s the real question: Are you using these because you’re stressed, have sleep apnea, or just can’t wind down? These meds don’t fix the root problem. They’re band-aids. But if you need a short-term solution while you work on better sleep habits, knowing which one fits your body matters. Some people swear by doxylamine for deep, uninterrupted sleep. Others find diphenhydramine works better for occasional use. Neither is magic. But one might be less likely to leave you feeling like you ran a marathon after eight hours in bed.

Below, you’ll find real comparisons, user experiences, and expert breakdowns of how these two sleep aids stack up against each other—and what to watch out for when you reach for the bottle.