"The lies and blatant fabrications in this interview given to a Russian state-sponsored TV station are an insult to the public's intelligence," Prime Minister Theresa May's spokesman said.
"More importantly they are deeply offensive to the victims and loved ones of this horrific attack. Sadly, it's what we've come to expect," the spokesman said.
"An illegal chemical weapon has been used in the streets of this country. We have seen four people left seriously ill in hospital and an innocent woman has died. Russia has responded with contempt," the spokesman said.
"The police have set out very clearly the evidence against these two men, they are wanted men and we have taken all steps to ensure they are apprehended and brought to justice in the UK if they ever again step foot outside of Russia," he added.
British security services named the two men as Alexander Petrov and Ruslan Boshirov but said these were likely to be aliases.
Interviewed on the Kremlin-backed RT news network, they denied any involvement with the murder attempt and said they were in Britain for tourism.
Skripal, who was jailed in Russia for betraying dozens of military intelligence officers in the 1990s, came to Britain in a 2010 spy swap.
He and his daughter Yulia collapsed on a bench in the English city of Salisbury on March, after coming into contact with the poison smeared on the handle of Skripal's front door, police said.
A policeman who came to their aid also fell ill and all three have since recovered.
A British couple, Dawn Sturgess and Charlie Rowley, came into contact with the same nerve agent in a town near Salisbury months later.
The nerve agent was in a perfume bottle that Rowley found in a charity bin and gave to Sturgess, police said.
Both fell critically ill and Sturgess has since died.
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