Mr Salmond said negativity from both sides had contributed to a “dispiriting” campaign, whereas the 2014 referendum in Scotland had been a “hugely uplifting experience” for many people.
His comments came during his regular phone-in programme on LBC radio, as the vote on the UK’s future in the EU draws close.
The Remain side have been accused by some of running a negative campaign, dubbed “Project Fear”, with warnings about the economic impact of a Brexit.
Mr Salmond’s SNP colleagues, including First Minister Nicola Sturgeon, have said attempts to “scare” the electorate into voting Remain could backfire.
Meanwhile, Leave campaigners have been criticised for their rhetoric on immigration, with Remain campaigners such as London Mayor Sadiq Khan branding it “Project Hate”.
Mr Salmond said: “I think this has been a dispiriting campaign, and it has been that because both sides have been engaged in negativity, the Remain side on the economy, the scaremongering, and the Leave side, disgracefully in my view, on immigration.
“It has been a pretty poisonous campaign.”
He added: “The Scottish referendum wasn’t like that. It doesn’t mean everybody behaved perfectly during the Scottish referendum, that doesn’t happen in politics. But for many people the Scottish referendum was a hugely uplifting experience.
“I would say it has been a pretty toxic campaign, and the responsibility for that should be on the campaign leaders.”