2009 losing to fellow Judoka gold medalist Hidehiko Yoshida by unanimous decision, but currently holds a record of 24–12–1.

[6] On 30 April 2011 Ishii returned to Judo to compete in the United States Championship in the open division; he won all the matches, securing the gold medal.

[7] After winning the gold medal, Ishii expressed his wishes to apply his talents in the sport of mixed martial arts (MMA) to the dismay of the Japanese Judo Federation.

[9] Japanese newspaper Sports Nippon then reported that Ishii would make his ring debut on December 31, 2009, at the annual K-1 Premium Dynamite!!

However, Ishii announced that he rejected FEG's offer, and was planning to pursue his MMA career in the US' Ultimate Fighting Championship (UFC).

[12] On September 14, 2009, it was announced that Ishii would make his MMA debut against fellow Olympian judo gold medalist Hidehiko Yoshida.

[14] Ishii, who was a large favorite in the fight, was dominated in the first round by the more-experienced Yoshida, taking many strikes including a right overhand that staggered the newcomer, along with a series of knees and uppercuts from the clinch.

[16] In June 2010, Ishii caused controversy during an MMA exhibition match on the undercard of X-1 World Events: Nations Collide in Hawaii.

[17] On September 25, 2010, Ishii fought Ikuhisa Minowa, a shoot wrestler known for facing much larger opponents, at Dream.16 and won via unanimous decision.

[21] Ishii continued to train at Black House in Brazil with notable fighters such as Lyoto Machida and Anderson Silva.

Since then he has trained at Mark Muñoz's gym Reign MMA, along with Mayhem Miller, Fabrício Werdum and other notable fighters.

Ishii then fought French kickboxing star Jérôme Le Banner in a mixed martial arts bout at the Dynamite!!

[25] However, he apparently decided against retiring from MMA as he went on to face former WEC Middleweight Champion Paulo Filho at Amazon Forest Combat 1 on September 14, 2011, in his light heavyweight debut.

The fight ended in a controversial draw, with journalists as well as the crowd agreeing that Ishii had won all three rounds.

[26] Satoshi Ishii next competed at Fight For Japan: Genki Desu Ka Omisoko 2011, where he met MMA legend Fedor Emelianenko.

[35][36] Ishii was expected to face PRIDE and Strikeforce veteran Sergei Kharitonov at M-1 Challenge 53: Battle in the Celestial Empire on November 11, 2014.

[42] After suffering back-to-back losses to Cro Cop, Ishii was scheduled to face Nick Rossborough at Inoki Genome Fight 3 on April 11, 2015.

[43] Ishii fought Will Penn in his final IGF appearance, at Inoki Genome Fight 4 on August 29, 2015.

[47] Ishii made his North American MMA debut against Quinton Jackson on June 24, 2016, at Bellator 157.

[50] Following his third consecutive loss, Ishii was scheduled to face the long-time mixed martial arts veteran Heath Herring at Rizin 2017 in Yokohama: Sakura on April 16, 2017.

[51] Ishii was scheduled to face Ivan Shtyrkov at RCC Boxing Promotions: Russia vs Japan on July 9, 2017.

[55] Ishii fought for the Serbian Battle Championship heavyweight title in his debut for the organization, against Tony Lopez at SBC 19 on December 1, 2018.

Ishii made his first SBC heavyweight title defense against Rodrigo Carlos at Serbian Battle Championship 20 on February 16, 2019.

[61] On January 1, 2019, Ishii revealed that he had signed a contract with Professional Fighters League, and he took part in the second heavyweight regular season.

[80] He was scheduled to make his kickboxing debut against the one-time cruiserweight title challenger Ryo Aitaka at K-1 World GP 2021: Yokohamatsuri on September 20, 2021.

[82] Ishii was scheduled to make his second professional kickboxing appearance against RUI at K-1 World GP 2021 in Osaka on December 4, 2021.

[89] Ishi made his professional boxing debut against Shuho Takayama (1–0) on August 14, 2022, as part of the "3150 Fight Vol 3" event.

[95] Ishii returned at Submission Underground 20 on December 30, 2020, to face Craig Jones in the co-main event.