In November 2018, Gillum narrowly lost the Florida gubernatorial election to Republican Ron DeSantis.

In the early morning hours of March 13, 2020, Gillum was present during an incident involving crystal meth at the Mondrian South Beach Hotel in Miami Beach. Specifically, two policemen responded to a cardiac-arrest distress call from the hotel just before 1 a.m.  When the officers arrived at the scene, they found a Miami Beach Fire-Rescue team already there, treating a man named Travis Dyson, an openly gay male escort, for a possible drug overdose. An acquaintance of Dyson, Aldo Mejias, told police that Andrew Gillum was also inside the hotel room under the influence of an unknown substance and had been vomiting in a bathroom. Officers later reported that when they had tried to speak with Gillum, he was “unable to communicate due to his inebriated state.” In a statement issued that same day to Miami Herald reporter David Smiley, Gillum said: “I was in Miami last night for a wedding celebration when first responders were called to assist one of my friends. While I had too much to drink, I want to be clear that I have never used methamphetamines.”

On March 15, 2020, Gillum announced that he would be entering a rehab facility, explaining that after his loss in the 2018 gubernatorial election, he “fell into a depression that has led to alcohol abuse.”

In February 2021, it was reported that Gillum in fact had paid Travis Dyson for sex on multiple occasions. Dyson alleged that he and Gillum had first gotten together on Grindr, a dating app for homosexuals. Dyson also said that during a number of their sexual encounters, both he and Gillum had taken Gamma Hydroxybutyrate, a drug that can heighten a user’s sex drive.