A video from the 17-year-old's celebrations surfaced this week, appearing to show rubbing something onto his gums.
But Khloe, 31, has blasted reports it was drugs. She tweeted: "You guys will make up anything. No! No one was doing coke at a graduation party in broad daylight with teenagers and 15 production cameras.
"We aren't as wild as you want to believe. We were taking Jell-O shots and you have to scrap the rim of the shot glass w ur finger to loosen up the jello in order to take it.
"Just say no to drugs kids! Drugs so not our style."
Their mother Kris, 59, threw the party for Kylie and 19-year-old Kendall, who graduated high school last year.
Sources close to the family have also rubbished the allegations of drug use at the event.
An insider told the Mirror: "All guests over 21 were asked if they wanted a Jell-O shot. There were dozens of cameras at this afternoon party so to suggest anything else is outrageous."
Also in attendance were Khloe and Kylie's nieces North West and Penelope Disick, and nephews Mason and Reign Aston Disick.