Tootoo, 52, became the first minister to quit Prime Minister Justin Trudeau's Cabinet since his Liberal government took power last autumn.
Tootoo, a member of Parliament for the sparsely populated northern territory of Nunavut, said he resigned his Cabinet post and would also be stepping down as a member of the Liberal caucus "in order to not distract from the important work of my colleagues."
"I have decided to seek treatment for addiction issues and ask for privacy at this time," Tootoo said in a statement.
He did not specify the type of addiction.
Trudeau said in a brief statement announcing the resignation that Dominic Leblanc would assume Tootoo's responsibilities while maintaining his role as government house leader.