Madoff is alleged to have lost 50 billion dollars of investors' money in a giant pyramid scheme that collapsed in the global financial crisis.
Santander said its investment fund Optimal has an exposure of 2.33 billion euros (3.1 billion dollars). The bank said it had also invested 17 million euros of its own funds in Madoff products.
French bank BNP Paribas also revealed it could lose up to 350 million euros (470 million dollars) in the scandal.
A BNP Paribas statement said the bank had no direct investment with Madoff's company but "it does have risk exposure to these funds through its trading business and collateralised lending to funds of hedge funds.
"If, as a result of the alleged fraud, the value of the assets of these hedge funds is nil, BNP Paribas' loss could amount to around 350 million euros.
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In Britain, a spokeswoman for Royal Bank of Scotland told AFP the bank had "some exposure" to Madoff, but declined to give details.
European media have said HSBC of Britain