A Glock 21 is Spencer's primary weapon throughout the film. The weapon is referred to as a "Glock 45" and appears to be full sized, so it is either a Glock 21, or a Glock 17 masquerading as a .45. However, in one scene, Spencer (Ashton Kutcher) is seen reloading his magazine with what are clearly .45 ACP rounds, so either the weapon is a Glock 21 or the film crew paid special attention to make another Glock appear to be a .45. Also in a shot of Vivian holding the Glock, there is a clear shot of the barrel, it is far too big to be a 9mm, even a 9mm barrel that has been bored out for the Hollywood BFA. It is obviously a .45 ACP Glock.
Colt 1911
Jen retrieves a blued Colt 1911 from a floor safe and points it at her friend Kristen (Casey Wilson) at the end of the film. Mr. Kornfeldt (Tom Selleck) is also armed with a M1911-type pistol when he confronts Spencer at the end of the film.
SIG-Sauer P228
A two-tone SIG-Sauer P228 is used by Olivia (Lisa Ann Walters) when she attempts to shoot Spencer, and later by Kristen at the end of the film.
An assassin disguised as a courier uses a Heckler & Koch UMP45 when attempting to kill Spencer. Spencer later commandeers the UMP to shoot at Olivia.
Heckler & Koch MP5SD
A MP5SD is used by Lily Bailey (Alex Borstein) in Spencer and Jen's home.
Rifles
Colt M4A1
Mac Bailey uses a M4A1 carbine while searching Spencer and Jen's home.
Mk 12 Special Purpose Rifle
Mac uses a Mk 12 Special Purpose Rifle (SPR) to shoot at Jen and Spencer as they return to their home. The rifle is fitted with a suppressor and fires on full auto, likely making it the same rifle that was seen in Live Free or Die Hard.