In order to understand exactly how long Nyquil lasts, it is absolutely vital to learn about the various ingredients in the drug. One of the ingredients found in Nyquil is Doxylamine, which is an antihistamine. This specific medication has a biological half-life or 6 to 12 hours. With this in mind, it is possible for the drug to remain in the system for a period of 12 to 24 hours. It should be known that the specifics will depend on a wide variety of different factors, including your age and metabolism.