McGregor is set for his first UFC fight since July 2021, facing Holloway in a non-title welterweight bout at UFC 329 in Las Vegas.
The matchup is a rematch of the pair's first encounter in August 2013, when McGregor defeated Holloway in Boston despite sustaining a torn knee ligament.
Previously, McGregor, now 37, had been scheduled to return in June 2024 against Michael Chandler but withdrew weeks before the event due to a toe injury.
Concerning anti-doping, McGregor served an 18-month ban after missing three drug tests within 12 months in 2024.
Combat Sports Anti-Doping (CSAD) said it reduced the length of the suspension after McGregor cooperated with the investigation.
The ban, backdated to September 2024, concluded in March 2025. Since then, he has been tested 11 times by CSAD, which is more than any other fighter currently on the UFC roster.
In November 2024, McGregor was found liable in a civil case and ordered to pay £206,000 (approximately $260,000) in damages to Nikita Hand, who accused him of rape at a Dublin hotel in 2018.
Another civil lawsuit filed by a woman who accused McGregor of sexual assault during an NBA game in Miami was dropped in December 2024, with no criminal charges pursued by authorities.
McGregor made his UFC debut in 2008 and holds a professional record of 22 wins and six losses.
He became the promotion's first simultaneous two-weight world champion, claiming the featherweight title in 2015 and the lightweight title in 2016.
Notably, his title fight stoppage of Jose Aldo in 13 seconds remains the fastest finish in UFC title fight history.
In 2017, McGregor faced Floyd Mayweather in a boxing match before returning to MMA.
His 2018 bout against Khabib Nurmagomedov became the best-selling UFC pay-per-view of all time, and his last victory came against Donald Cerrone in 2020.
Now, as he prepares for Holloway, McGregor faces a difficult test.
Holloway, 34, is known for competing consistently at the highest level of lightweight competition in recent years.
The card for UFC 329 will also feature Liverpool's Paddy Pimblett against Frenchman Benoit Saint-Denis, British flyweight Lone'er Kavanagh against Brandon Royval, and the unbeaten Luke Riley against Kai Kamaka at featherweight, rounding out an exciting night of fights.