The Sala dei Giganti is located in the southern corner of the Palazzo del Té. The walls and the ceiling of the room are painted with a single continuous scene of giant figures. It is an apocalyptic catastrophe into whose centre the viewer enters. The room's decoration represents Jupiter punishing the giants for having dared to oppose his power and for bringing their rebellion to his domain.

The giants are attacking the gods, trying to storm Olympus, piling mountain onto mountain, until Jupiter causes the boulders to fall with his lightning, and the attackers are buried beneath them. From the summit of Mount Olympus, the father of the gods hurls his thunderbolts at the earth, sweeping away the giants and the awkward pile of rocks intended to support their ascent into the heavens. The pantheon of pagan divinities that surround him are for the most part paralysed with fear. The giants are ill-proportioned but muscular, with grotesque, desperate faces, and they are depicted struggling amid or trying to escape the dramatic collapse of rocks and fictive architecture that Giulio Romano imagined.