He suspended Holy Roman Emperor Frederick II for not carrying out the Sixth Crusade that he had promised at his coronation on 22 November1220.
He then excommunicated Frederick, and threatened to depose him when he complained; Frederick's army marched on the Pope, lost in the field, and Frederick had to beg for absolution.
In June 1232, a popular revolt in Rome caused Gregory to flee to Anagni.
Frederick came to his aid, and the two reconciled to a point, but in 1239 hostility broke out between the them, leading to a war that lasted until Gregory's death.
He strongly opposed heresy, supporting the belief that they not only opposed the Church, but because kings were chosen by God, heretics were traitors to the civil order, as well.
Assisted King Louis IX to suppress the heretical Albigensians in France, and supported any attempt to turn heretics over to civil authorities.
Established the Monastic Inquisition in April 1233, appointing Dominicans to investigate accusations of heresy in France.
He worked for a reunion of the Latin and Greek Churches, and in 1232 even got an acknowledgement of papal primacy, but the Greeks felt they were often poorly treated by the west, and they then fell into dispute over whether the host must be leavened or unleavened, and talks ended.
He supported the University of Paris, and intervened to prevent philosophy from supplanting theology.
Gregory appointed fourteen cardinals during his papacy including the men who would later be PopeInnocent IV and PopeAlexander IV.