With Phineas: Phineas and Isabella are great friends. They always help eachother. Phineas is Isabella's long dream love. Is clueless Phineas feelings to Isabella, but in some cases he has shown also to be in love of her.
With Ferb: Isabella and Ferb has a normal friendship. In the episode ''Quamtum Bogaloo'' is shown that Isabella can marry Phineas or Ferb. Is clueless!!
With the Fireside Girls: Isabella and the fireside girls are the best friends. They share secrets and always are toghether when need to get a patch or be in trouble.
With Candace: They aren't like Best Friends, but they share they crushes. Candece knows about her crush on Phineas and Isabella of her crush on Jeremy.
With Baljeet: They are great friends. Baljeet seem to love Isabella as how he proposed himself to be Isabella's date while discovering what the rare machine Phineas and Ferb found does (''What do it do?)
With her mother: She have a normal Mother and Daugther relationship with her mother.