The New Zealand international has played 12 seasons with the joint-venture club and will finish his career as a one-club player.
Nightingale, 31, is the last remnant of the 2010 Premiership side coached by Wayne Bennett.
“It’s a very proud and solemn day for me to be announcing the end of the career. I am extremely grateful for everything that the Dragons and the game has done for myself, and what I’ve been able to achieve,” Nightingale said con the club’s website.
“There are so many people to thank for what’s been a special journey. From Renown United through to the junior reps to now, through the highs and lows and great successes I’ve had, I’m just so thankful for this incredible journey.
“There have been so many great seasons personally. To be recognised for so many different reasons that are celebrated at the Dragons, they all still sit on my mantelpiece very nicely.
“The 2010 grand final win was the highlight for me and my family. There are so many fond memories from that day and the season as a whole. Although now is great time to reflect, there are still plenty of memories to be made this season yet.
“However I’m also look forward to more family time with my second child on the way. My wife Bianka has sacrificed a lot for my career. She’s been selfless by supporting me throughout my career, while also building one of her own.
“It’ll be good to rearrange my priorities now and put her career first as well as continue to build the Elite Athlete Business School and help fulfil its potential alongside my business partner and the EABS family.”