"I still feel uncomfortable when I'm watching him," Gutfeld said Wednesday.
"When he's feisty, I like it because it's funny when he gets exasperated and tells stories and stuff," he continued. "But when he loses his place and closes his eyes, you see that he's frustrated and it's no longer funny to me. It makes me sad. It’s gaffes about mental confusion, dates, memories, what happened ... we all see that with people we know."
Gutfeld was responding to Biden's latest gaffe, in which the candidate passionately declared during Tuesday's Democratic debate that Sen. Bernie Sanders' support of a law that protects firearms manufacturers from being held liable for gun violence deaths had lead to "150 million" deaths since 2007.
Between 2007 and 2017, 373.663 Americans were killed by firearms in the U.S. According to the Center for American Progress, that number includes both violent firearm deaths and unintentional or accidental deaths.
Earlier in the week, Biden mistakenly said he was running for the U.S. Senate instead of the presidency during a speech at a South Carolina Democratic Party dinner.
Gutfeld questioned why Biden's campaign wasn't stepping in to help the struggling candidate, joking that if his co-host Dana Perino had "spinach in her teeth, someone tells her."
"But there's nobody over on Joe's side saying stuff," he explained.
Perino agreed, and pointed to Biden's unprofessional campaign events as proof of a weak team, compared to billionaire and former New York City Mayor Michael Bloomberg.
"His campaign has not set him up for success," she said. "Look at the advance team for Bloomberg, it looks beautiful ... all the lighting's great and almost every shot that Biden has had, it does not look professional. He has not been served well by that."
"I agree that his team has not served him well moving forward," Katie Pavlich chimed in.
"They’ve been very focused on a single demographic of voters in a single state ... it's great if he wins on Saturday, but it seems like they've been very narrowly focused, with blinders on, about trying to pull out South Carolina."
Pavlich added that Biden's campaign is "hoping that somehow this changes the momentum" against Sanders, who currently leads the delegate count as the race heads into Super Tuesday next week, before adding: "I don't see it happening."
Fox News' Vandana Rambaran contributed to this report.