On 6 February 2019, Palladino was definitely appointed manager of Depor for the 2019 campaign.[4] He achieved promotion to the Primera División after finishing second in his first season, helping the side to return to the top tier after 15 years.[1]
On 8 November 2022, after qualifying Maldonado to their first-ever continental championship (2023 Copa Libertadores), Palladino left the club, and was named in charge of Chilean Primera B side Santiago Wanderers.[5] He left the club on 22 May 2024, and returned to his home country with River Plate Montevideo on 17 June.[6]