Rishi Sunak has said he finds it "very upsetting" that his wife has faced criticism over shares she owns in a tech company operating in Russia.
The chancellor compared his feelings to those of film star Will Smith, whose own wife was mocked at the Oscars.
But he joked: "At least I didn't get up and slap anybody, which is good."
Mr Sunak's wife Akshata Murty owns shares thought to be worth more than £400m in Indian firm Infosys, founded by her father, Narayana.
The chancellor has himself come in for several days of criticism over last week's Spring Statement, which opposition parties say did too little to address the spiralling cost of living.
He told the BBC's Newscast podcast: "I think it's totally fine for people to take shots at me. It's fair game. I'm the one sitting here and that's what I signed up for."
But he added: "It's very upsetting and, I think, wrong for people to try and come at my wife, and you know, beyond that actually, with regard to my father-in-law, for whom I have nothing but enormous pride and admiration for everything that he's achieved.
"And no amount of attempted smearing is going to make me change that because he's wonderful and has achieved a huge amount."
Mr Sunak also mentioned England cricket captain Joe Root, whose team lost a Test series to the West Indies at the weekend, and Mr Smith, who slapped comedian Chris Rock in the face when he mocked his wife, Jada Pinkett Smith, over her alopecia at Sunday's Oscars.
He told BBC political editor Laura Kuenssberg: "Someone said, 'Joe Root, Will Smith, and me - not the best of weekends for any of us.'
"But I feel, on reflection, both Will Smith and me having our wives attacked - at least I didn't get up and slap anybody, which is good."
Multinational software giant Infosys has kept what it calls a "small team of employees based out of Russia" following the country's invasion of Ukraine.
Labour and the Lib Dems have said Mr Sunak has questions to answer about whether his family benefits from the shareholding at a time when he is calling for UK businesses to divest from Russia.
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