Cartier's initial encounters were marked by trade and interactions with the Mi'kmaq and St. Lawrence Iroquoians. However, the kidnapping of Domagaya and Taignoagny set a precedent of distrust and exploitation.

Cartier received hospitality from Chief Donnacona and the Iroquoians at Stadacona. However, his decision to ignore Donnacona's warnings and travel to Hochelaga, followed by the kidnapping of Donnacona and others, strained relations. He also took advantage of their knowledge of how to treat scurvy, without appropriate reciprocity.

On his third voyage, relations with the Iroquoians deteriorated significantly. The establishment of Charlesbourg-Royal, coupled with the probable death of Donnacona in France (and the failure to return the kidnapped Iroquoians), likely fueled resentment and hostility. There were attacks and skirmishes between the French and the Iroquoians.

Cartier's actions contributed to a legacy of distrust between Europeans and the Indigenous peoples of Canada. His exploitative behavior and disregard for Indigenous sovereignty had long-term consequences for future interactions.