Don't forget that "girl" is neuter in German, so you actually can't use "sie" there, at least in the singular. Ein Mädchen ist es ("it").

But you figure it out by context, including the conjugation of the verb (sie ist - "she is", sie sind - "they are"). In rare cases it can be confusing for the native speakers, and they might ask each other (or you) for clarification - whether you mean the "them" sie or the "her" sie.