The company has been undergoing a restructuring as it tries to revive sales amid criticism that its food is too high in fats, sugars and salt.
Demand also was hit by mad-cow disease, which put many consumers off eating meat.
Under Mr Cantalupo's leadership McDonald's recently revised its menu, offering healthier options such as salads and fresh fruit.
McDonald's spokeswoman Anna Rozenich said the company could not immediately say who was taking over Mr Cantalupo's responsibilities.
"We're focusing on Mr Cantalupo and his family," she said.