The Old Lady have chosen ex- Italy head coach the veteran manager to take the helm until the end of the season.
Spalletti takes over from the Croatian manager, who was let go following the loss to Lazio recently.
The former boss came on board in March as Thiago Motta's replacement but exited following a seven-month stint at the end of an eight-match winless run.
Spalletti guided Napoli to the Serie A crown in 2022-23 prior to assuming the Italy role, after the team's failure to reach the 2022 World Cup under former boss Roberto Mancini.
He helped them qualify for Euro 2024 exiting in the last 16 stage against Switzerland.
Nonetheless, Italy dismissed Spalletti in June after a World Cup qualifying defeat by Norway, as Italy faced the possibility of not making a third World Cup in a row.
Spalletti's managerial career includes Inter Milan, Roma, and Udinese in Serie A and won the Russian Premier League twice with Zenit St Petersburg.
Massimo Brambilla served as interim manager for Juventus for their 3-1 win against Udinese on Wednesday moving them to seventh position in the league - six points behind leaders Napoli after nine games.
Their Champions League campaign sees them in 25th place in the group stage, after recording one defeat and two ties in the initial three fixtures.