Among the distinguished thinkers with whom Brucioli developed relationships there, the names of Francesco Cattani da Diacceto, Luigi Alamanni, and Niccolò Machiavelli stand out.
During his stay in Lyons, he seems to have absorbed many of the religious ideas of the German reformers, adopting moderately Lutheran theology in his translation of the Bible, a work which some said relied heavily on Martin Bucer.
However, as a political moderate and strict believer that the Dominican friars of San Marco should keep out of state affairs, he quickly fell afoul of the dominant Savonarolan faction, being exiled from the city in 1528.
Having been first denounced in 1548 and found guilty of disseminating heretical materials (but not of heresy), he fled to the tolerant court of Ferrara and the protection of the duchess, Renée of France.
In 1549, we find him directing overtures to Cosimo I de Medici hoping to be granted a stipend in exchange for regular reports on political activities.