On February 16, 2008, Slice fought Tank Abbott in the main event at EliteXC: Street Certified. He won by KO 43 seconds into the first round due to strikes. At the fight his weight was announced at an all-time low of 234 lb (106 kg), a far cry from his street fighting days of 280 lb (130 kg).
On May 31, 2008, Slice fought in the main event of the first ever mixed martial arts event shown on prime time network television, EliteXC: Primetime. Though one of the judges had each fighter winning one of the first two rounds, Slice's opponent James Thompson won both on total points by repeatedly taking down Slice and grounding and pounding. In the opening seconds of the third round, however, Slice threw a haymaker to Thompson's left ear, which ruptured Thompson's cauliflower. This was soon followed by three unanswered punches to a standing Thompson, which led to a referee stoppage and the controversial win for Slice. Fellow EliteXC competitor Brett Rogers was particularly critical of Slice's victory, calling Slice's performance "garbage" in a post fight interview. Frank Mir was also a critic of Slice, stating in an interview that "every time Kimbo Slice fights, it sets (mixed martial arts) back".
On October 4, 2008, a Kimbo Slice vs. Ken Shamrock fight was supposed to take place at the BankAtlantic Center in Sunrise, Florida as part of CBS' Saturday Night Fights. However, Shamrock received a cut to the left eye during a warm-up only hours before the fight was to take place. This left the head of fight operations, Jeremy Lappen, to choose a replacement for the fight. Options were Seth Petruzelli, Aaron Rosa and Frank Shamrock. Slice's team stated they did not want him fighting Frank no matter how much money was offered to them, so Lappen decided that Petruzelli was the best option for the main event. Slice agreed to take the fight after receiving a raise in pay, and took in $500,000. Petruzelli defeated Slice by TKO 14 seconds into the first round of the bout.
On October 23, 2008, the Florida Department of Business and Professional Regulation concluded its investigation of the bout and found no wrongdoing. By the end of October 2008, EliteXC was forced to file for bankruptcy. Many in the mixed martial arts community, including Jay Thompson, executive consultant to the company, attributed EliteXC and ProElite's failure due to Slice's loss to Seth Petruzelli.
Slice was featured on The Iron Ring, a television series airing on BET that features MMA prospects. Slice was part of the selection process for the participants. He made his official acting debut when playing the character Bludge on Nickelodeon's 2008 holiday special, Merry Christmas, Drake & Josh. He also played an inmate named JC in 2009's fightning film Blood and Bone.