The Raiders, who have since moved to Las Vegas, announced Henderson's passing on Wednesday.
"The Raiders Family is heavy hearted following the passing of Mario Henderson, who was a third-round draft pick and played four seasons with the Silver and Black. Everyone will miss Mario's sense of humor and passion for football and life. The prayers of the entire Raider Nation are with Mario's family and loved ones at this time."
No cause of death has been announced.
The New England Patriots picked Henderson 91st overall in 2007 but soon dealt him to the Raiders in a draft-day trade.
He played four seasons for the Silver and Black and started 28 of his 44 games. The ex-Florida State Seminole manned the starting left tackle spot for all 16 games in 2009.
He played at Lehigh Senior High School in Florida prior to his FSU tenure.
Numerous people offered their condolences and remembrances of Henderson on Twitter, including New York Giants kicker Graham Gano, the NFLPA Former Players organization and James Chaney, a former teammate of Henderson's who now coaches the Lehigh Senior High School football team:
Chaney also spoke to Fox 4:
"A lot of Florida State people are reaching out; a lot of local people are showing love. And Mario was just one of the nicest big 6'8" human beings that you can ever run across."
"And I'm really, really sad and along with thousands of others about the loss today."
Henderson also spent time in the San Diego Chargers' training camp and played on teams in the United Football League, Arena Football League and Indoor Football League.
Larry Gary, a near four-decade Lee County football coach who mentored Henderson, also offered his thoughts to Adam Regan of the Fort Myers News-Press.
"All of my insides hurt right now. It doesn't seem real. He was such a loving person. There's no better person I could be associated with."
Per Regan, Henderson was most recently working with special needs students at Dunbar High School (Florida) in addition to working as an assistant for the football team.