The Kiwi will team up with Guy Martin for the one-lap electric race on Wednesday, June 4.
Morecambe’s McGuinness has been ruled out of the TT after sustaining injuries including a badly broken right leg in a crash during practice at the North West 200.
A statement issued by Mugen said Anstey, who rode for the team in 2014, 2015 and 2016, was the ‘natural choice to turn to’. The 48-year-old was not initially retained by the Japanese team this year after Lincolnshire rider Martin was given the nod following his deal with the Honda Racing team.
Expectations are high this year that the first 120mph lap of the Mountain Course will be achieved by an electric machine. McGuinness currently holds the lap record at 119.279mph.
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Anstey has won 11 times at the TT and has finished on the podium more than 30 times.
The veteran racer will again spearhead the Padgett’s Honda team in the Superbike, Supersport, Superstock and Senior races along with Manx rider Conor Cummins, who missed the North West through injury.