The parents of Isetnofret are not known. She must have married Ramesses II even before he came to the throne as her eldest children already appear in scenes from the time of Seti I. She had at least three sons and one daughter. Her children include:
Prince Sethi and Princess Nebettawy have been suggested as further children of Isetnofret, but they are more likely to be the children of Nefertari.
Titles
Queen Isetnofret's titles include: Hereditary Princess, Great of Praises, King’s Mother, Mistress of the entire Two Lands, King’s Wife, Great King’s Wife
Life
Isetnofret is known from several inscriptions and small statues. She is not well attested before year 25 of Ramesses II. Most of the items and scenes mentioning Queen Isetnofret seem to be associated with her sons Ramesses, Khaemwaset and Merenptah.
Isetnofret is shown on a family stela from Aswan. The upper register shows Ramesses II, Isetnofret and Khaemwaset before the god Khnum. The lower register shows Prince Ramesses, Merneptah and Princess Queen Bintanath.
A family stela from the Speos at West Silsila shows Ramesses II, Isetnofret and Bintanath with a much smaller Khaemwaset before the godsPtah and Nefertem. The lower register shows Prince Ramesses and Prince Merenptah.
A Statue with Prince's Figure. Her son is named on the statue: the Sem-Priest and King's Son Khaemwaset.
A Statue group with Sons : A "hetep-di-nesu" offering for the King's Son, Sem priest of Ptah, Khaemwaset and the royal scribe, Generalissimo and King's Son Ramesses. The text mentions Queen Isetnofret.
The Head of a Statue : On right shoulder the name of Isetnofret appears.
A naophorous Statue of Prince Khaemwaset mentions his mother. On the dorsal pillar it reads: Iunmutef-priest, born of the Great Royal Wife Isetnofret, the Sem-priest of Ptah Khaemwaset.
Relief for offering for Prince Khaemwaset in Horemheb's Speos. The text above the prince reads: Sitting at table, making purification with natron and reading out the menu, every good offering, for the King's Son of Usermaatre Setepenre, born of the Great Royal Wife, Isetnofret, the Sem-priest Khaemwaset.
Shabtis from Middle cemetery of Abydos: One of these has a cartouche of Queen Isetnofret.
West Silsila: Rock shrine of Merneptah. A scene depicts Ramesses II, Queen Isetnofret with sistra before Taweret, Thoth and Nut.
A daughter of her son Khaemwaset was named after her. It is possible that this Isetnofret was Merenptah's wife, not her aunt Isetnofret II. A possible daughter of Merneptah also bears this name.