In the video published on Twitter, Macron, dressed in shirt sleeves, can be seen walking towards a crowd of on-lookers, who were behind a barrier.
As he went to shake the hand of one man, who was wearing a mask, the man reached out and slapped him.
The man could be heard shouting out “Down with Macronia” in French before he delivered a slap to Macron’s face, reported the Telegraph.
The president’s security quickly intervened to pull the man to the ground and move Macron away from him.
Well-wishers could be heard screaming immediately after the incident while some burst out in laughter.
The incident took place while Macron was on a visit to the Drome region in south-eastern France, where he met restaurateurs and students to talk about how life will return to normal after the pandemic.
Two people were arrested in connection with the incident, according to broadcasters BFM TV and RMC radio.
Officials in the country have shown solidarity with the president including Far-left leader Jean-Luc Mélenchon and Prime Minister Jean Castex.