The Targum writes that the significance of the number (75,000) of dead indicates that this is the number of Amalek’s descendants.
R’ Dovid Feinstein notes that although this seems like a large number, mathematically the 75,000 enemies would only be a little under 600 people from each of the 127 states.
Another significance to this number is noted by the Midrash (Bireishis Rabba 39:13) where it points out that Esther was 75 years old when she became queen of Persia. In her merit, these 75,000 enemies were killed.
Perhaps this is reiterated in the fact that the Nachal Eshkol noted that the im hakollelgematria of Hadassa (5+4+60+5(+1) = 75) is equivalent to the Ben Ish Chai’s calculation of the gematria of the Yehudim (10+5+6+4+10+40=75).