Isabella d'Este (3 October 1635 – 21 August 1666) was Duchess of Parma, and second wife of Duke Ranuccio II Farnese. She was the paternal grandmother of Elisabetta Farnese.

Isabella was a daughter of the Duke of Modena Francesco I d'Este and Maria Caterina Farnese, daughter of Ranuccio I Farnese, Duke of Parma. She was the sister of two Dukes of Modena, Alfonso IV d'Este (1634–1662) and Rinaldo (1655–1737). At the death of her mother, her father married again twice.

After the death of his first wife Marguerite Yolande of Savoy, Ranuccio II married in 1663 his cousin Isabella. But the couple only met on 18 February 1664, when Isabella arrived in Parma. For this occasion, a grandiose celebration and musical spectacles were organised. The couples had three children all of which would survive childhood. Only the latter Odoardo, would have issue; he was the father of Elisabeth Farnese, queen of Spain and ancestor of most modern royalty.

But the birth of her son proved fatal to Isabella, who died of complications nine days later on 21 August, at Colorno. She was the paternal grandmother of Elisabeth Farnese, Queen of Spain. She was buried at the Sanctuary of Santa Maria della Steccata in the city of Parma on the 23 August. Her husband remarried in October 1668 to her sister Maria d'Este. By her he had a further seven children as well as the last two Farnese Dukes of Parma.

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