World number one Djokovic, the champion in Paris in 2016 and chasing a 19th Grand Slam title, faces 93rd-ranked Ricardas Berankis.
Djokovic defeated the 30-year-old Berankis at last year’s tournament.
When his opponent isn’t revelling in the delights of being Lithuania’s only player in the top 400, he unwinds by spearfishing in the waters of the Baltic nation.
Djokovic, bidding to be the first man in more than half a century to win all four majors on multiple occasions, can reach the last 16 for a 12th consecutive year with victory over the sea-loving Lithuanian.
The top seed has made the third round without problems, enjoying comfortable straight set wins in the first two rounds.
Nadal, seeded three this year and chasing a 14th French Open and record 21st Grand Slam, faces fellow left-hander Cameron Norrie.
The Johannesburg-born Briton claims that had he not made a living from tennis he would have been an estate agent.
The 25-year-old, ranked 40, is enjoying a breakout season on clay, reaching the finals in Estoril and Lyon.
He has played Nadal twice already this season, losing at the Australian Open and Barcelona on clay where the Spaniard won in straight sets for the loss of just five games.
“I’ve learned that he’s actually a human being,” said Norrie.
“But it can be absolute carnage going into his forehand.”
Nadal made the third round with a 17th win in 17 meetings with childhood rival Richard Gasquet.
Roger Federer, locked on 20 majors with Nadal, is aiming to reach the round of 16 at a Grand Slam for the 68th time.
The 39-year-old Federer, who won his only French Open title in 2009, tackles Germany’s 59th-ranked Dominik Koepfer in the evening session.
Djokovic and Federer are seeded to meet in the quarter-finals.
Wins on Saturday for the pair will bring that match-up one round closer.
In a wide open women’s draw, defending champion Iga Swiatek has made the third round for the loss of just seven games.
The Pole has not dropped a set at the tournament since her fourth round run in 2019 when she lost to 2018 champion Simona Halep.
On Saturday, the eighth seed takes on Estonia’s 30th-seeded Anett Kontaveit who dropped just two games in her quickfire defeat of last home player Kristina Mladenovic in the second round.
Kontaveit is bidding to reach the last 16 for the second time.
There are two all-American ties on Saturday.
Fourth seed Sofia Kenin, the highest-seeded player left in the event after the exits of Ashleigh Barty, Naomi Osaka and Aryna Sabalenka, faces Jessica Pegula.
Coco Gauff, seeded 24, faces 13th-seeded Jennifer Brady who was a shock finalist at the Australian Open this year.
Seventeen-year-old Gauff is the youngest player in the last 32 since 16-year-old Michelle Larcher de Brito in 2009.
Gauff also is the youngest American to reach the third round at Roland Garros since 16-year-old Serena Williams in 1998.
Fifth seed Elina Svitolina, a three-time quarter-finalist, is up against Barbora Krejcikova, the winner on clay in Strasbourg on the eve of Roland Garros.