The Russian second seed, who won the US Open in September, threw away a two-set lead over Rafael Nadal in an epic final at Melbourne Park that lasted almost five-and-a-half hours.
A snarling Medvedev continued his battle with local fans, having first drawn their ire when he said those who booed him during a second-round win over Nick Kyrgios "probably have a low IQ".
The 25-year-old repeatedly berated chair umpire John Blom for not silencing the crowd at crucial moments during Sunday night's showdown, urging him to "take control".
"Step up, man, it's the final of a grand slam!" Medvedev shouted at Blom after dropping serve to fall behind 3-2 in the fourth set.
"(Saying) 'please' is not enough. They are idiots. With idiots, 'please' doesn't work. Step up."
Australian umpire Blom threatened to have security eject fans who called out when the combatants were serving.
Medvedev, who struggled with leg cramps and looked increasingly weary as Nadal fought his way back into the match, gave the crowd sarcastic applause several times after his serve was broken.
The 2-6 6-7 (5-7) 6-4 6-4 7-5 loss was the second time Medvedev had fallen after leading a grand slam match by two sets, following a first-round defeat to Pierre-Hugues Herbert at Roland Garros in 2019.
In one last moment of controversy, Medvedev appeared to mutter the word "boring" as Tennis Australia chair Jayne Hrdlicka spoke during the presentation ceremony.
But the world No.2 was far more gracious at the microphone.
"(The match) was insane. I think the level was very high," Medvedev said.
"You (Nadal) raised your level after two sets (to win) a 21st grand slam.
"I thought he was going to get tired and maybe he did just a little, but still won the match."
It was Nadal's second Open title, the two successes separated by four defeats in the final at Melbourne Park.
The Spanish great sympathised with his beaten opponent.
"I know it's a tough moment. Daniil, you are an amazing champion," Nadal said.
"I have been in this position a couple of times at this tournament.
"I have no doubt you will have this trophy a couple of times in your career.
"It has been one of the most emotional matches in my tennis career and to share the court with you is just an honour."
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