The article aims to examine the cases of political impact of Italian regions in the EU in the post-Brexit period. Steps of the new “yellow-green” government, which came to power in June 2018, towards political impact on the regions balancing between right- and left-wing populist economic and social reforms are assessed. The hypothesis of the article is that despite huge differences in political, economic, and social conditions, all cases illustrate that regions of Italy will focus mostly on paradiplomatic activities rather than mutating towards protodiplomacy. Special attention will be given to the northern regions of Italy, where paradiplomacy has been developed since the beginning of the 1990s.