The Old Lady have named previous Italian national team manager the veteran manager to take the helm for the remainder of the campaign.
Spalletti steps in for his predecessor, who was let go after the Serie A side's defeat by Lazio on Sunday.
The former boss came on board in March to replace Thiago Motta but exited following a seven-month stint at the end of an eight-match winless run.
Under Spalletti, Napoli clinched the Serie A championship in 2022-23 before taking charge of Italy, after the team's failure to reach the 2022 World Cup during Roberto Mancini's tenure.
He secured their spot in Euro 2024 exiting in the last 16 stage against Switzerland.
However, Spalletti was sacked by Italy in June post a qualifying defeat against Norway, with the Azzurri at risk of missing out on a third consecutive World Cup.
He has previously coached Inter Milan, Roma, and Udinese in Italy's top flight 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 which left them seventh in Serie A - trailing leaders Napoli by six points after nine matches.
Their Champions League campaign sees them in 25th place in the group stage, with one loss and two draws in their first three games.
