In 1999 he was elected in the city council of Bologna, as a member of the Christian democratic Union of the Centre; from 1999 to 2004 he served as assessor of budget in the cabinet of Giorgio Guazzaloca, the sole centre-right mayor that ruled Bologna since the Second World War.[3]
In 2009, he was a candidate for the presidency of the Bologna Province, gaining 4.6% of votes; while the following year, he ran as UDC candidate to the Presidency of Emilia-Romagna, however, Galletti arrived only fourth behind the centre-left governor Vasco Errani, the centre-right candidate Anna Maria Bernini and the Five Star Giovanni Favia. During the campaign he announced his support to nuclear power, which has been a long-time debate in Italy.[4]
On 26 April 2012, Galletti was elected leader of the Union of Centre in the Chamber of Deputies, replacing his political mentor Pier Ferdinando Casini.[5]
In the general election in the following year, Galletti ran in the coalition With Monti for Italy, led by incumbent Prime Minister Mario Monti, a centrist technocrat, but he did not succeed in being elected. However, after few months he was appointed undersecretary to the Education Ministry, in the Enrico Letta's government.
His nomination was harshly criticized by many green associations due to his support to nuclear power; Monica Frassoni, a former MEP, accused Galletti of being only known as the "tax advisor of Pier Ferdinando Casini".[7]
During the Italian rotating presidency of the EU Council in 2014, he led to the modification of the European legislation on GMOs, allowing each state to have decision-making autonomy on the cultivation of genetically modified organisms on its territory.[8] During the same period, he advised the council of EU towards a more restrictive regulation on the use of single-use shopping bags.[9]
In November and December 2015, Galletti participated in the UN Climate Change Conference in Paris, better known as COP 21. The conference brought a global agreement on the reduction of climate change, the text of which represented a consensus of the representatives of the 196 parties attending it.[11]
On 12 December 2016, when Renzi resigned as prime minister after the constitutional referendum, Galletti was confirmed as Environment minister by the new prime minister Paolo Gentiloni.[12]
In the run-up of the constitutional referendum the Union of the Centre chose to campaign for "No", while Galletti, Casini and other centrist deputies were among the keenest supporters of "Yes". After the referendum, Casini, Galletti and Gianpiero D'Alia launched a new party, known as Centrists for Europe.[13]
Galletti decided not to run in the 2018 general election, which then saw a large defeat of the centre-left coalition, to which his new party as part of the Popular Civic List belonged, (although Casini was reelected) and a plurality for the centre-right led by the populist League of Matteo Salvini, but also a strong showing for the anti-establishment Five Star Movement.[14][15][16]