Combine the calamari and buttermilk in a large bowl, cover, and refrigerate for 30 to 50 minutes.
Heat the oil in a large, deep pot or your deep fryer to 375 degrees F (190 degrees C).
In a medium bowl, add the flour, salt, paprika, pepper, onion powder, and garlic powder. Whisk with a fork to combine.
Working with one piece at a time, remove the calamari from the buttermilk and dredge in the flour. Repeat until all of the pieces are coated in flour.
Add 8 to 10 pieces of the calamari to the hot oil and cook until golden brown, 2 to 3 minutes. Drain on paper towels. Repeat with the remaining calamari and serve immediately.