The second seed came through 7-6 (7/4), 6-4 against his 96th-ranked opponent to extend his record on indoor hard courts in his own country to 18-1.
That run also included the title in Metz in 2023 as well as a run to the Paris Masters final last year where the left-hander lost to Alexander Zverev.
"I didn't know him well and he was very, very good," said Humbert of his opponent on Sunday.
"I am very happy to retain my title here. I am very proud too because I was a little nervous at the start of the tournament. It means a lot to win in France."
Medjedovic, the 2023 ATP NextGen champion, was chasing his first Tour-level title.
