Smith, 50, is best known for providing the voice of Lisa Simpson in the long-running Fox animated series 'The Simpsons', reported Entertainment Weekly.
She will have a live-action role in 'The Mindy Project' as an OB-GYN who is blackmailed by Dr Mindy Lahiri (Mindy Kaling).
Mindy Lahiri uses the blackmail in order to get boyfriend Danny Castellano's (Chris Messina) mother (Rhea Perlman) in for an appointment.
'The Mindy Project' has also lined up Allison Tolman, 'Grey's Anatomy' producer Shonda Rhimes and 'Reno 911!' star Niecy Nash for guest appearances.