The duchess of Mantua Margherita Paleologo Gonzaga is an understudied figure of the Italian sixteenth century's religious, political and cultural life. Through the analysis of her unpublished correspondence, this contribution investigates Margherita's relationship with some of the most influential representatives of the so-called Italian Evangelism, such as the Genoese cardinal Federico Fregoso, the bishop of Verona Gian Matteo Giberti and the Capuchin preacher Bernardino Ochino, who in 1542 fled from Italy religionis causa. The example and teaching of these men fostered Margherita's interest in the main spiritual themes and debates of the time, and led her to unconventional positions. For example, along with her brother-in-law, cardinal Ercole Gonzaga, she got involved in the reform of religious life within the Duchy, especially focusing on female monasteries; moreover, she financed the publication of books dealing with the topic of mental prayer. As a result of her actions, Margherita found herself at the centre of a huge network of relationships, both with men and women who lingered within the Roman Church, such as the Dominican friar Reginaldo Nerli, and with persons who were linked to the circles of religious dissent – it is the case of the printer Gabriele Giolito – or would even prove heterodox, as the mentioned Ochino or the hebraist Francesco Stancaro.