On 8 November 2015, Appendino officially announced her candidacy for mayor of Turin in the 2016 Italian local elections.

She did not run for the 2021 Italian local elections and was replaced as mayor by Stefano Lo Russo of the Democratic Party.

In October 2017, the Prosecutor's Office of Turin started an investigation on Appendino for falsity in a public document in connection with the city's 2016 budget.

[5] In November 2017, an investigation started into lack of safety during incidents at Piazza San Carlo, where one person died and more than 1,500 were injured in the 2017 Turin stampede during the UEFA Champions League final match between Juventus and Real Madrid on 5 June.

They must respond for not having taken sufficient measures to combat smog pollution that since 2015 has led the Turin air to be repeatedly the worst in Italy.