But Demetriou told AFL.com.au on Friday the AFL would be a "much cleaner" competition by round one, saying the League's and the Australian Sports Anti-Doping Authority's joint investigation into the ACC's findings would convince any players using performance-enhancing drugs to stop.
"I think every supporter is entitled to feel disappointment and I can understand them questioning when they go out to watch their team in round one: 'Is this all above board?'," Demetriou said.
"It's an absolutely logical and natural reaction. My response is that, firstly, this issue doesn't involve the majority, if not the high percentage, of our players and clubs.
"The second thing is, as of yesterday, and with the awareness that's been raised, I've got absolutely no doubt that if people were thinking of doing something tomorrow that they've been doing, they'll have stopped.
"They'll have stopped because they're on notice. And we've got information, as have ASADA, and we're now conducting our investigation and we will start the process.
"So I'm very confident that by round one ... what we'll be seeing on the field will be much, much cleaner than it may have been in the past."
The ACC released its report, Organised Crime and Drugs in Sport, on Thursday, revealing that the use of the new-age performance-enhancing drugs peptides and human growth hormones was widespread among Australian sports stars.
Two days earlier, Essendon had asked the AFL and ASADA to investigate "concerning" information it received on supplements given to some of its players last season.
Demetriou said confidentiality provisions prevented him from discussing the specific evidence compiled by the ACC as part of its year-long investigation.
As such, he could not answers questions on the likely penalties Essendon would receive if Bomber players were found to have taken performance-enhancing drugs, and on whether other clubs were likely to be implicated in the AFL-ASADA investigation.
Demetriou also would not comment on whether Essendon might be entitled to a reduced penalty given it had voluntarily come forward before the ACC's report was released. But he said the World Anti-Doping Agency's code provided for reductions of the standard two-year suspension for drug use when a party provided "substantial information".
There has been speculation that the AFL-ASADA investigation into Essendon could, at worst, lead to the club being unable to field a team at some stage in 2013.
But Demetriou said the AFL did not fear the outcomes of the investigation.
"We're prepared for what lies ahead in the report, we're prepared," he said.
"I think it would be terribly, terribly sad if after the investigation some fine people, decent people, have been let down and if players have been told certain things and that has implications for them or others in clubs."
Demetriou was hopeful disillusioned fans would not stay away from games and turn off their TVs, saying clubs and players were entitled to the benefit of the doubt while the investigation was ongoing.
"I understand fully if supporters are feeling disappointed, I understand that," he said.
"But I would urge everybody to put the game first. The game is much bigger than ... we who work here, much bigger than players and officials that come and go.
"The game is much more important and it means so much to so many people, so I hope that people have their faith in the game restored."
Nick Bowen is a reporter with AFL.com.au. Follow him on Twitter: @AFL_Nick