Barca are in the midst of a fine campaign and look set to cruise to the title domestically, as they sit nine points clear of Atletico Madrid with eight games to go.
Messi has been a major part of that, scoring 26 goals and setting up another 12 in what has been a tremendous year.
And Manolas, who will face Messi in Camp Nou on Wednesday for the first leg of their Champions League quarter-final tie, agrees with Pep Guardiola's recent comments about the Argentina superstar.
"Guardiola is right when he says there's no way to stop him [Messi]," the Greek centre-back told Il Giornale.
"Even if you could fix that somehow and maybe block him off, there are 10 others that can hurt you. Of course, Barcelona are still something else without Messi. We'll have to do our best."
The last time Roma met Barca in the Champions League, back in November 2015, the Serie A side were hammered 6-1 and Manolas, who played the entire game, knows they got it all wrong that day.
"Tactically speaking, we got that game wrong," Manolas said. "We pushed too high up and they found space easily.
"Now we won't have to go there with the fear of conceding so many goals. We respect Barcelona, but we're aware of our strengths.
"We showed in the group stage that we're a good team. Wow we have a double-header against a very strong opponent. They're favourites, but when you play 11 against 11, you never know."