The corruption allegations came in a video by opposition campaigner Alexei Navalny, viewed by millions on YouTube.
Mr Medvedev's properties include a vineyard in Italy, a mountain villa, and two luxury yachts, it is alleged.
"They pick up any old tosh, nonsense, about me or my acquaintances, and people I've never heard of," he said.
It is the first time he has commented on the claims published by Mr Navalny's anti-corruption network on 2 March.
Mr Navalny said the prime minister profited from a complex business network which concealed "bribes" by using offshore schemes and charity foundations.
The claims stirred up mass protests which saw thousands of Russians march against the government in several cities on 26 March. Hundreds of demonstrators were detained, many of them young supporters of Mr Navalny.
The following day a court jailed Mr Navalny for 15 days for disobeying a police officer.
Mr Medvedev said the "provocative" video was "expensively produced - financed by private sponsors" and "aimed at achieving a specific political result".
"They lure young people via social media, and those youths come out with certain slogans, unfortunately in violation of the law. In essence, they expose them to the machinery of law enforcement, and those youths suffer as a result."
He was speaking to workers at a bacon factory in the Tambov region, south of Moscow.
Mr Navalny - a fierce critic of President Vladimir Putin and his Kremlin associates - plans to run for the Russian presidency next year.
Mr Medvedev said he had "strong nerves" which protected him from such attacks. "If I reacted each time to such attacks I simply wouldn't manage to get on with my job as normal."

It's not as easy as you think, but then try pairing them all with a character from The Simpsons.
That's just what Brian Quinn from Londonderry has done for the Irish Simpsons Fans Facebook group.
Like all great ideas, Mr Quinn said it started out small and then kind of escalated.
"I probably had one pun in my head - I think it might have been DoneGil first," he told BBC News NI.
"I started scribbling more down and I think I had about 17 and I thought: 'I might as well do all 32 now.'
"My girlfriend was watching Grey's Anatomy or something, so I just got out the laptop and started messing about."
By Thursday evening, his post was closing in on 1,000 likes.
He said he was surprised at which ones seemed to be the most popular.
"It's funny, the last couple that I thought of probably got the most likes and I thought they were kind of scraping the barrel," said Mr Quinn.
"They were the Cork one - Hank Skorkio - and the ones for Meath and Westmeath."
Ireland Simpsons Fans started on Facebook in January 2016 and was the brainchild of Jack Leahy from Dublin and Paul Loughran from Belfast.
Mr Quinn is now the page moderator for the site.
As for his own personal favourite, a bit of hometown favouritism might be at play.
"I'm from Derry and I actually think the Derry and Kerry - Sherri and Terri ones are the funniest and the cleverest," he said.
Russian Prime Minister Dmitry Medvedev has dismissed as "nonsense" allegations that he has secretly accumulated a vast fortune including country estates.
[NEXT_CONCEPT]
Can you name all 32 counties of Ireland?