Doxylamine is one of the many sedating antihistamines used by itself as a short-term sedative, and in combination with other drugs as a night-time cold and allergy relief drug. It is also used in combination with the analgesics paracetamol (acetaminophen) and codeine as an analgesic/calmative preparation, and is prescribed in combination with vitamin B₆ (pyridoxine) to prevent morning sickness in pregnant women.

Doxylamine is a member of the ethanolamine class of antihistamines and has anti-allergy power superior to almost every other antihistamine on the market, with the exception of diphenhydramine (Benadryl). It is also the most effective over-the-counter sedative available in the United States and is more sedating than some prescription hypnotics. One study found that doxylamine succinate was more effective than the barbiturate phenobarbital for use as a sedative.

The dosage required to induce hypnosis (sleep) can be as low as 6.25 mg, but is usually effective in dosages of up to 25 mg. Higher doses are not recommended by the United States Food and Drug Administration, although single dosage recommendations of up to 50 mg are common in some countries, including Australia, where it is marketed under the names Restavit and Dozile. A recent placebo-controlled, double-blind randomized trial found the formulation of doxylamine and pyridoxine marketed as Diclectin to be effective in controlling nausea and vomiting due to pregnancy.