Propolis is one of the mixtures with the widest biological activity among natural products used in complementary medicine. HSV-1 is a highly contagious and endemic virus. Available drugs are insufficient for recurrent HSV-1 infections. Therefore, new approaches to treat HSV-1 infections are still being developed. In this study, it was aimed to investigate the inhibition effect of ethanolic Anatolian propolis extracts obtained from the Eastern Black Sea Region (Pazar, Ardahan, and Uzungol) on HSV-1. In addition to the total phenolic (TPC) and the total flavonoid content (TFC), the phenolic profiles of the extracts were analyzed by HPLC-UV. The antiviral activity of the extracts were tested by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), quantitative Real Time Polymerase Chain Reaction (qRT-PCR), and plaque reduction tests, and the results were evaluated statistically. It was determined that the total amount of phenolic substances varied between 44.12 and 166.91 mg GAE/g, and the total flavonoid content of the samples varied between 12.50 and 41.58 (mg QUE/g). It was shown that all propolis samples used in the current study were effective against HSV-1, but the higher phenolic compounds contained in the samples showed the higher activity. The results show that ethanolic propolis extracts are promising candidates for HSV-1 treatment.