In a large bowl, soak the shrimp in buttermilk for at least 30 minutes to tenderize.
In another bowl, combine flour, Cajun seasoning, garlic powder, onion powder, paprika, salt, black pepper, and cayenne pepper.
Heat about 1 inch of vegetable oil in a large skillet over medium-high heat.
Remove shrimp from buttermilk, allowing excess to drip off, then dredge each shrimp in the seasoned flour mixture, shaking off any excess.
Fry the shrimp in batches for about 2-3 minutes on each side, or until golden brown and crispy. Remove and drain on paper towels.
In a separate bowl, whisk together mayonnaise, sour cream, Dijon mustard, lemon juice, Cajun seasoning, salt, and pepper to make the creamy sauce.
Serve the crispy Cajun shrimp hot with the creamy sauce on the side for dipping.