The Spaniard is upset with comments made by Roselyne Bachelot, who was formerly Minister for Health and Sport.
The 14-time Grand Slam winner, 29, says he will sue anyone else who alleges “something similar in the future”.
Nadal says he is tired of the allegations and is no longer prepared to let them pass unchallenged.
“A minister of France should be serious,” he said. “This time is the time to go against her. We are going to sue her.
“This is going to be the last one, because I’m going to sue her. I am tired about these things. I let it go a few times in the past. Not any more.”
Bachelot, 69, served as Minister for Health and Sport from 2007 until 2010, under the government of former president Nicolas Sarkozy.
She made the allegations about Nadal last week, when addressing Maria Sharapova’s failed drugs test.
“When you see a tennis player stopping for months, it’s because there’s been a positive control,” said the French politician.
Nadal has already spoken out about the speculation surrounding him.
Following Sharapova’s admission last week of a failed test, the former world number one said: “I am a completely clean guy.
“I have never had the temptation of doing something wrong.”
Nadal has never failed a drugs test but has been the subject of speculation that he dopes.
In 2011, former French Open champion Yannick Noah wrote a newspaper article saying Spanish sporting success was due to doping.
A year later, a satirical French TV show featured a life-size likeness of Nadal filling up his car’s gas tank from his own bladder before being pulled over by traffic police for speeding.
Then in 2013, Belgian former professional player Christophe Rochus questioned Nadal being able to dominate the 2012 French Open and then be injured two weeks later at Wimbledon.