After his retirement, Giampaolo was signed as scout for Serie B side Pescara Calcio, and successively promoted as assistant coach in 2000. In 2001, he was appointed assistant coach of Serie C1 side Giulianova Calcio, in support of Adriano Buffoni. Both left on April 2002, despite the team was fully involved in a fight for a playoff placement, citing bad relationships with the club's management. In 2002–03, both Buffoni and Giampaolo signed for Treviso of Serie C1, leading the team to an immediate promotion to Serie B and saving the team from relegation the following season. In 2004–05, Giampaolo moved to Ascoli, where he again acted as assistant coach of unknown manager Massimo Silva. This was often cited as a trick in order to allow Giampaolo to coach the team, as he was not in possess of a valid coaching licence at the time. The season ended in a good sixth place, which allowed Ascoli to play promotion playoffs, where it was defeated by Torino Calcio. However, following a serie of cancellations by the federation, Ascoli was admitted to play Serie A the next season, and both Giampaolo and Silva were confirmed to coach a team built in only two weeks, with the only goal to maintain a place in Italian top division. In February 2006, Giampaolo was disqualified for two months by the Italian Football Federation for having acted as first team head coach without a valid coaching licence. Successively, Giampaolo was admitted to join the Coverciano coaching course, and, after having saved Ascoli from relegation, he was announced as coach of Cagliari Calcio. In September 2006, Marco Giampaolo was involved in a freak training ground accident, the 39-year-old boss was hit on the head by a wayward ball and, despite continuing with the training session, developed symptoms of concussion soon after. The coach was taken to hospital as a precautionary measure. On 17 December 2006, after a 3–1 away defeat to Udinese in a league match, Cagliari boss Massimo Cellino announced to have sacked Giampaolo, citing coach's loss of confidence with the team. However, on 26 February 2007 Cellino decided to sack Franco Colomba and reinstate Giampaolo back at the Cagliari head coach position. After having led Cagliari to avoid relegation, he was confirmed for the 2007–08, but he was sacked again on 13 November and replaced by Nedo Sonetti, leaving the rossoblu in last place with nine points. He was later called once again to return at the helm of the rossoblu, following the dismissal of Sonetti, but he ultimately rejected the offer, citing his unwillingness to do so. He successively rescinded his contract with Cagliari, and in June 2008 was announced head coach of Siena for the 2008–09 season, who was dismissed on 29 October 2009. On 30 May 2010 Giampaolo was appointed to replace Siniša Mihajlović as head coach of Catania. After an unimpressive first half of season, Giampaolo and Catania parted company on 18 January 2011. On 4 June 2011, Cesena announced that he will be appointed head coach, replacing Massimo Ficcadenti who left the club by mutual consent despite keeping the club in Serie A. On 30 October 2011 he was sacked because of bad results, leaving Cesena at bottom of Serie A table with just 3 points. In July 2013 he was named new head coach of Serie B club Brescia. He left Brescia by mutual consent on 25 September 2013 after having stated his intention to quit the club following a heated home loss to Crotone and Giampaolo's disappearance for three days after confronting with the club supporters. On 9 June 2015 it was announced that Giampaolo was named new coach of Empoli. On 4 July 2016, he became the new manager of Sampdoria on a 2-year contract, succeeding Vincenzo Montella. After the 2018-2019 season, Giampaolo terminated his contract with Sampdoria. On 19 June 2019, Giampaolo signed with Serie A club Milan a contract until 2021, with an optional one-year extension. He was sacked on 8 October 2019, after seven matches in charge with three wins and four defeats.
