No, they are not interchangeable.
A guardian is someone who protects someone or something in a more abstract or moral way than a guard, who protects something physically.
So a legal guardian can be someone who looks after a child in the place of a parent. A religious figure might be described as a guardian of their faith.
A guard could operate in the context of a prison or a castle.
A guard could also be an object, like a mouth guard.