The Russian, a losing finalist at the last two Australian Opens, crashed 6-3, 6-4 to a dominant Djokovic on Friday evening in the Adelaide International semi-finals.
Despite the defeat, he said he felt "really great" and was in a good place heading into the opening Grand Slam of the year after an under-performing 2022, where he dropped to seventh in the world rankings.
"Novak is different league - 21 Slams. That's all we have to say. But generally positive and I need to stay positive because the first Slam is coming," he said after the defeat.
"You have to believe in yourself," he added. "I honestly say that before every match.
"Every time I play them (Djokovic and Rafael Nadal), before the match the only thought is I have to win, I have to try my best to win.
"I managed to do it. Rafa I think I beat only once, but still I managed to do it. I had some tough matches against him. Against Novak I won a Slam."
Since defeating Djokovic for the 2021 US Open title, Medvedev has been beaten three times by the Serb, who is back in Australia after missing last year's Australian Open because of his vaccination status.
Medvedev almost beat Nadal at Melbourne Park last year in an epic final before going down in five sets.
While Djokovic and Nadal pose a serious threat to Medvedev's quest for a second Grand Slam title, he got a boost last week when world number one Carlos Alcaraz pulled out injured.
The Russian said it was shame, but he was sure the young Spaniard would bounce back.
"It's a pity. He's one of the best players in the world," he said.
"The way he played at 18 years old, he could be a little bit kind of Rafa, Novak, Roger (Federer) kind of guy. But he still has 19 slams to win.
"I'm sure he's going to come back stronger."
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