Is it safe to mix unisom with NyQuil?

No, do not take these together. Both of these have an ingredient which causes sleepiness. If you check the label --- you will see that it is the same drug (diphenhydramine). You would be taking a double dose of this, which could cause trouble breathing or trouble waking up in the morning. If you are over 60, you could run a risk of falling from taking a double dose.