Legal highs 'mexxy' and 'black mamba' are to be made illegal class B drugs with users facing up to five years in jail.
The drugs are to be permanently banned after drugs advisers found they posed dangerous risks to health, Crime Prevention Minister Jeremy Browne said.
"People who take 'legal highs' are taking serious risks with their lives because often they do not know what they are taking and the drugs may contain harmful substances," he added.
The move comes after methoxetamine, or mexxy, was linked to two deaths and police warned of the "life-threatening effects" of black mamba.
As class B substances under Misuse of Drugs Act 1971, users will face heavy fines and up to five years in prison, while suppliers could be jailed for up to 14 years.
Mr Browne said: "The UK is addressing the harm caused by 'legal highs' by outlawing not just individual drugs, but whole families of related substances that have the potential to cause serious harm."
Police warned people not to take mexxy, which is sold as an alternative to ketamine, after the bodies of a 59-year-old woman and a 32-year-old man were found in Leicester and Melton Mowbray on February 11 and 12 respectively.
It was the first substance to be put under a temporary ban earlier this year, but within hours the Speaker's wife Sally Bercow said the government's plans made her tempted to try it before it was too late.
Mrs Bercow assured her more than 45,000 followers on Twitter she would not actually buy any, but admitted she was tempted and "now obsessed with the stuff, despite never having heard of it 1/2 hr ago".
And Prime Minister David Cameron pledged to crack down on legal highs amid fears over black mamba.
Tory MP Nadhim Zahawi said in March that Warwickshire Police had warned him of its "life-threatening effects" after a 13-year-old child in his Stratford on Avon constituency took the drug.