The 52-year-old actress will be reprising her role as compassionate foster care worker Rita Henricks in two upcoming episodes, reported Digital Spy.
O'Donnell's character developed a close bond with the troubled foster child Callie (Maia Mitchell) in her previous guest stint.
Her return appearance will air on the ABC Family show in August.
'The Fosters', which is produced by Jennifer Lopez, was recently honoured at the 25th GLAAD Media Awards for its portrayal of an interracial lesbian couple raising children.
ABC Family premieres the second season of 'The Fosters' on June 16.