The two men arrested aged 21 and 29 were taken into custody Nov. 9 in Bell, California, by Huntington Beach police detectives.
One of the men had 20 pounds of methamphetamine when he was picked up and a search warrant was issued, which led police to more drugs and guns, the Orange County Register reported.
The names of the suspects were not immediately available.
Police took in 317 pounds of methamphetamine, nearly 40 pounds of cocaine and fentanyl, and two handguns.
Detectives began the investigation in October, the paper reported.