The previous outbreaks of syndrome coronavirus 2 (SARS-CoV-2) are indications of the need for effective antiviral agents to mitigate disease severity and future outbreaks. In this context, natural products such as propolis have gained attention for their antiviral properties, particularly due to the rich composition of bioactive compounds. Propolis derived from Tetragonula sapiens, a stingless bee species, has shown promising pharmacological properties, including antimicrobial, antioxidant, and anti-inflammatory effects. Therefore, this study aimed to investigate the antiviral potential of T. sapiens propolis from Indonesia against SARS-CoV-2 using both in vitro and in silico methods. In silico analysis was conducted by molecular docking to evaluate the binding interactions of 30 bioactive compounds from T. sapiens propolis against RNA-dependent RNA polymerase (RdRp), a key enzyme in viral replication. The phytochemical substances found were 1,5-Dimethyl-4-[[(2-methyl-6 phenylthieno[2,3-d] pyrimidin-4yl) hydrazinylidene] methyl]pyrrole-2carbonitrile, Isocalopolyanic acid, Glyasperin A, Yucalexin B7, and Sulabiroin A. Additionally, in vitro experiments assessed the efficacy of T. sapiens propolis in inhibiting viral activity in Vero E6 cells. The results showed that propolis extract had virucidal properties, directly inactivating the virus. This study identified T. sapiens propolis as a promising natural source for antiviral drug development and future therapeutic applications. © (2025), (Faculty of Engineering, Universitas Indonesia). All Rights Reserved.