Jonilla S Marak (65) and her grand-daughter Bikame (4) died yesterday at a hospital in Tura, they said.
Police said the family had cooked wild mushroom on Sunday and fell ill shortly after consuming it.
Bikame's seven-year-old brother, Tebiangku and his mother Anila (35) are in hospital, they said, adding their condition is stated to be critical.
Death from mushroom poisoning in Garo Hills region came less than a week after a similar incident in East Khasi Hills district, in which six members of a family died after consuming wild mushroom.