Does benadryl (diphenhydramine) make mucus thicker?

Mucus: Depends....If you have a ton of mucus sitting in the sinuses, then yes, it can thicken up the large quantity of mucus already there. If you are trying to dry up the mucus forming, it is a good alternative. There is much debate. Overall, Benadryl (diphenhydramine) is a poor choice since it lasts only 4-6 hours and causes extreme drowsiness. Go with a 24-hour non-sedating antihistamine.