During his pontificate vigorous measures (e.g. burning at the stake, confiscation of property) were taken against proponents of Lollardy which had found acceptance in Germany, England, and other parts of Europe. Efforts were made to reform corrupt practices in the various monastic orders such as collecting fees from persons visiting holy sites and the exhibiting of faux relics of saints.
John Wycliffe's 19 Reformation articles on church-related items as he wrote in his On Civil Dominion and 21 proposed reformation articles of Johannes Klenkoka's Decadecon were submitted to Pope Gregory XI in the early part of the 1370s. Gregory formally condemned fourteen articles of Decadecon in 1374  and nineteen propositions of Wycliffe's On Civil Dominion in 1377.
His return to Rome on 17 January 1377, is supposedly attributed in part to the stirring words of Catherine of Siena. This had been attempted by Gregory's predecessor, Urban V, without success. The project was delayed by a conflict between the pope and Florence, known as "the War of the Eight Saints" for the "Eight for War," the Florentine magistrates responsible for the conduct of the war. The pope put Florence under interdict during 1376.
Gregory XI did not long survive this trip, dying on 27 March 1378. He was buried the following day in the church of Santa Maria Nuova. After his death the College of Cardinals was pressured by a Roman mob that broke into the voting chamber to force an Italian Pope into the papacy. The Italian chosen was Urban VI. Soon after being elected, Urban gained the Cardinals' enmity. The cardinals returned to Avignon and in 1378 elected a French pope, the antipope Clement VII.
Subsequently, the Western Schism created by the selection of rival popes forced the people of Europe into a dilemma of papal allegiance. This schism was not fully resolved until the Council of Constance (1414–1418) was called by a group of cardinals. The council boldly deposed the current popes and in 1417 elected Martin V as their successor. The chaos of the Western Schism thus brought about reforming councils and gave them the power over who was elected, replacing (for a time) the College of Cardinals.