The 35-year-old, from Cowplain, was in the crash with a Mercedes at around 11.56pm on Friday in Milton Road, Cowplain, near the parade of shops.
Members of the public rushed to start CPR but the man was pronounced dead at the scene by paramedics.
His family have been told, and now police are investigating.
The Mercedes driver has been spoken with, officers are not looking at any other vehicles having been involved, and no arrests have been made.
A Hampshire police spokesman said: ‘Prior to the collision, the moped is reported to have driven along London Road, from the direction of Widley, before turning on to Hambledon Road and then Milton Road.
‘Officers would like to hear from anyone who saw what happened, but are particularly keen to capture any footage from dash cams, doorbell cameras and CCTV of the moped between London Road and Milton Road, in the moments leading up to the collision.
‘If you can help us with our enquiries, please contact us on 101, quoting 44210292771.’
Report any information online at hampshire.police.uk