Isola joined the Entain board in February 2016 and served on the Audit, Remuneration and Environmental, Social and Corporate Governance committees.
Entain said Isola had left the business in order to focus on other opportunities.
A legal expert, Isola is a senior partner at Gibraltar-based law firm Isolas, having helped found and launch the business in September 1982.
Isola has also served as a non-executive director of BetVictor since May 2014 as well as at Gibraltar International Bank since June 2015.
Aside from this, he is chairman of the Fiduciary Group and commissioner of the Gibraltar Financial Services Commission a part-time basis.
“On behalf of the board, I would like to thank Peter for his significant contribution and commitment to Entain over the last six years,” Entain chairman Barry Gibson said. “We wish him well for the future.”
The departure comes after Entain earlier this month also announced revenue of £3.83bn (€4.59bn/$5.03bn) for its 2021 financial year, representing a 7.6% increase on the previous year.
Earlier this month, Entain said that it was to target growth in new markets to build on the growth it recorded in 2021.
During an earnings call to discuss its financial results, Entain CEO Jette Nygaard-Andersen gave an insight into the company’s plans to expand its territory in countries such as Canada and Brazil.
Entain recently completed the acquisition of Avid Gaming in Canada, while Brazil passed legislation to legalise land-based and online gambling in the country at the end of February.