If something is unfamiliar to you, you know nothing or very little about it, because you have not seen or experienced it before.
She grew many wonderful plants that were unfamiliar to me.
她种了很多我从未见过的奇异植物。
If you are unfamiliar with something, you know nothing or very little about it.
She speaks no Japanese and is unfamiliar with Japanese culture.
她不会说日语,也不熟悉日本文化。