Human immunodeficiency virus (HIV) is a genus of Lentivirus that triggers opportunistic diseases in the human body. HIV-1 has been a major problem for the world community for a long time and triggered a pandemic. HIV-1 antiviral drugs with the mechanism of inhibiting specific proteins have been found but have some harmful side effects for patients. Back to nature solutions can be used to solve these problems. Natural ingredients can be used as an alternative treatment for the treatment of HIV-1 infection allegedly more effective and minimal side effects. Antiviral candidate natural ingredients such as Garcinia mangostana L. with compounds consisting of Mangostin and Garcinone, the potential of Garcinone compounds is currently still unidentified. This study aims to reveal the potential of Garcinone derivative compounds from Garcinia mangostana L. as HIV-1 antiviral through the mechanism of reverse transcriptase inhibition with an in silico approach. The method used in this research is in silico simulation such as druglikeness analysis, molecular docking, chemical bond identification, and molecular stability. Garcinone A from Garcinia mangostana L. can be an HIV-1 antiviral candidate with a good molecular mechanism of inhibiting HIV-1 RT activity because it produces more negative binding affinity than the control drug and triggers stable binding interactions on the target.