The Reds and Barca will meet in a highly-anticipated Champions League semi-final, with the first leg taking place at Camp Nou on Wednesday.
Jurgen Klopp's side will naturally be focused on Barca's talisman, who is in the midst of another standout campaign.
Messi has 46 goals in all competitions in 2018-19, with Barca having already clinched the Liga crown as well as having a Copa del Rey final to look forward to.
Klopp will try to devise a plan to slow down the Argentine star, but Zenden says that stopping Messi is much easier said than done.
"It is impossible to stop him by using a single player," Zenden told Goal.
"It makes no sense speaking about that, especially because he plays in a lot of different positions in every game.
"We saw it once more against Levante. It makes no sense speaking about how to stop him because you can't stop him."
Virgil van Dijk will be one member of Liverpool's backline who will be charged with attempting to thwart Messi, with the Dutchman having been named the PFA Player of the Year for his excellent performances in 2018-19.
But Zenden has cautioned that it will take much more than just one in-form defender to make a difference against Messi.
"He already played versus Barcelona with Celtic," Zenden said of Van Dijk.
"Playing against Messi needs teamwork but the main problem with that is Barcelona always have advanced passing lines and it makes the situation even harder to defend.
"That's why Barcelona always score, it is not only because they are so good, it is because their style is almost impossible to defend.
"But Liverpool is another offensive team with their own style. I think it is impossible there is a 0-0 [draw] in any game."
Zenden spent two seasons at Liverpool between 2005 and 2007. The Dutchman is well aware of what a Champions League title would mean for the fans at Anfield.
"I only have good memories of this club, they have a great history full of success and there is a lot of suffering as well," Zenden said.
"They have united all the fans and you can feel it in the Champions League nights especially. You have to live it, you have to feel it to be able to understand it."