The piece, which was undamaged, was left with white cream smeared across its protective glass.
The perpetrator, seen wearing a wig and lipstick, urged people to "think of the Earth" while being led from the scene.
The incident on Sunday was described by witnesses as being "jaw-dropping".
Louvre visitor Luke Sundberg, from the US, saw it all unfold. "The crowd begin gasping and we looked up and some man in a wheelchair [dressed] as an old lady ran up to the painting and started punching it before smearing cake all over it," the 20-year-old told the PA news agency.
"It took about 10 to 15 seconds for the security to actually take the man away, but the crowd seemed to panic a little bit.
"It was jaw-dropping, it was a lot to take in considering how historic Mona Lisa is... the moment was once in a million."
The activist, who was also seen throwing roses in the gallery, was escorted out by security. "Think of the Earth," he declared.
"There are people who are destroying the Earth. Think about it. Artists tell you: think of the Earth. That's why I did this."
A 36-year-old man was detained and sent to a police psychiatric unit, the Paris prosecutor's office confirmed on Monday, adding it had started an investigation into the damage of cultural artefacts.
The Renaissance painting had glass installed in the 1950s to protect it after an acid attack.