World No 1 Djokovic was shocked by Medvedev as he fell to a 6-3, 4-6, 6-2 defeat in the quarter-finals.
The Serbian was expected to storm through the tournament to meet Rafael Nadal in the final.
But for a third consecutive event, Djokovic was sent home early in a massive blow to his French Open preparations.
However, the 31-year-old has given a number of reasons for his loss.
“Look, it is the first tournament of the season on clay and maybe the lower-ranked guys play one tournament before,” he said.
“That can be one of the reasons.
“Others is you’re part of the same sport as everybody else and it happens that you have a bad day.
“I cannot speak on behalf of Sacha [Zverev] or Dominic [Thiem, who also departed in the early rounds] here but the conditions are quite slow here.
“The balls are different this year and they bounce really high.
“We had four different days with four different conditions.
“Very sow low bounce, heavy conditions. The you had a lot of wind and all of a sudden very hot.
“It does affect your game a lot and it is a big challenge to adjust to that.”
Despite his early exit, Djokovic is not worried about his recent form.
The 15-time Grand Slam winner believes everything is still on track for him to peak at the French Open.
“It is expected in a way for me to peak right at the French Open because that’s what i’m aiming for,” he added.
“This is only the first tournament on clay and it is a long season so let’s see how we go.”