When Republicans talk about entitlements, Matthews said Democrats should "tell the voters they're going after Social Security and Medicare."
GOP-backed efforts to require voter ID, Matthews said, should be described as voter suppression of minorities.
And voters should be reminded that pro-life candidates are "coming after abortion rights."
"You've got to get out there and put a very strong, bold picture on what the Republicans would like to do and say that's what they're going to do," the MSNBC talking head said on "Morning Joe."
And although that might help Democrats salvage a few seats in the House, Matthews is pretty much convinced the party's majority in the Senate is as good as gone.
The outcome in this week's special election in Florida, he said, does not augur well for President Obama's party.
“It’s going to be very hard to hold the Senate — I think the Senate goes,” he said. “I think we heard from the Ghost of Christmas Future this week. They’re going to lose the Senate."
The commentariat overwhelmingly declared David Jolly's victory over Alex Sink in Florida's 13th congressional district to be a bad omen for Democrats. The district voted for Obama twice, and polls early in the race showed Sink with solid leads.
Republicans, meanwhile, have been eager to characterize the race as a referendum on Obamacare, but Karl Rove urged his ideological brethren not to oversimplify Jolly's win.
Matthews isn't one to shy away from prognosticating. Last August, he predicted that Rand Paul will be the GOP's presidential nominee in 2016.
"You watch," Matthews said confidently. "This is what I do for a living."