The actress will join the NBC series as a character named Maryanne, a wheelchair-bound nosy neighbour who becomes suspicious of the Munsters, according to TVLine.
The role will see Grant reunite with her Pushing Daisies and Wonderfalls director Bryan Fuller, who is also overseeing Mockingbird Lane.
The show will star Jerry O'Connell as father Herman Munster, Portia de Rossi as his wife Lily Munster, and comedian Eddie Izzard as Grandpa.
30 Rock's Cheyenne Jackson has been cast as a scout master who falls in love with Lily.
O'Connell has pledged that Mockingbird Lane will be "completely different" from and "a little darker" than The Munsters.
Watch the opening to The Munsters below: