Two hundred years later when French explorers ventured into those same areas there was no one to be found.
The plague in the North American Continent took between 80-90% of the population. It is the reason they were conquered so easily—there were relatively few of them left.
Aside from NOT coming west, I am not sure what could have been done to prevent that. And the Settlers in North America had little to do with that.
The Settlers in North America killed them outright with firearms; but the damage had been done by disease 100 years earlier.
Eventually—even if Cortez had not infected the Mexican people, trade would have commenced as the Western Europeans reached the resource rich North American Continent. Literally, with first contact, he diseases would would have been spread. The deaths would have occurred in the 1600s rather than the 1500s.
This is what happens.
Two hundred years later when French explorers ventured into those same areas there was no one to be found.