Matu'u, 34, joined from Gloucester in the summer of 2018 and played 30 times for the club, helping Irish return to to the Premiership in 2019.
Naholo, 30, played four times in the 2019-20 but missed all of the current season with a serious knee injury.
Tom Homer and Theo Brophy-Clews have already announced their retirement.
Harry Elrington, Nic Groom, Charlton Kerr, Andrei Mahu and Vladimir Podrezov are also leaving.
"On behalf of everyone at London Irish, I would like to thank the departing players for all their hard work and efforts for the Club," Exiles' director of rugby Declan Kidney told the club website.
"Tom retires after making more than 100 appearances for the club, with Theo and Harry both reaching the 50-game milestone. All three of them have been fantastic servants for the club, on and off the field.
"Motu, Nic and Andrei have all worked tremendously hard to get London Irish get to where we are at present.
"Waisake, although not able to play as much as he wanted, has been a brilliant influence on our back three players and so is leaving with a long-term positive affect on the club.
"Charlton and Vladimir will not be as well known by our supporters, as unfortunately injuries and opportunities did not fall their way. But both are great people, and we thank them for their work rate and energy that they both brought to the squad."