Substitute will change every occurrence of the Old_Txt in the search string, unless you give it a Instance_Num field. I'm going to guess that's not what you're asking.
Substitute doesn't work like CountIFS or SumIFS, where you can have multiple comparisons. Nothing stops you from nesting substitutes into a single cell:
=SUBSTITUTE(SUBSTITUTE(TestText,"old","new"),"fox","cat")
Excel evaluates this from the inside out, per normal. The "old"/"new" change happens first.
Depending on what type of text strings you're working with, nesting could give some unexpected results.