Nadal, a known stickler for routine and order, arrives at a revamped court Philippe Chatrier which has been 80% rebuilt for this year's tournament, but the 32-year-old said he will not be affected by the changes.
He is generally a slow starter but should not have any problem getting past his first-round opponent, Germany's Yannick Hanfmann.
The 27-year-old, who turned professional only four years ago, has never advanced past the opening round of a Grand Slam but he feels no pressure facing the championship favourite.
"I'll know a lot about him and maybe he doesn't know as much about me," he said in an interview on the Roland Garros website.
"I've been playing well. I've got a big game... So if my serve and return works, I can definitely do some damage."
While the crowd may be overwhelmingly in favour of Nadal, it is not something that affects Hanfmann, who has a hearing impairment.
"It's an advantage on court," he added. "Maybe on Chatrier, it'll be an advantage because I don't hear that much that's going on."
In the other half of the draw, Djokovic begins his quest to hold all four Grand Slam titles for the second time in his career when he takes on Poland's Hubert Hurkacz.
Djokovic became the first man since Australia's Rod Laver in 1969 to hold all four Grand Slams in 2016 when he won his only French Open title.
Three-times Roland Garros champion Serena Williams is looking to win her 24th Grand Slam singles title and she takes on Vitalia Diatchenko who has never progressed to the third round.
Dominic Thiem, who comes into the tournament having won titles in Barcelona and Indian Wells this year, will be in action on court Suzanne-Lenglen against American Tommy Paul.
Stan Wawrinka, a winner in 2015, will be the star attraction on court Simonne-Mathieu when he takes on Jozef Kovalik while French veteran Richard Gasquet faces Mischa Zverev.
(Reporting by Rohith Nair in Bengaluru; Editing by Toby Davis)
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