Cistus laurifolius L., Cistaceae, has long been used for traditional treatments against various skin diseases in Turkey. The study was designed to observe an antiviral effect against anti-HSV-1 activity and to develop an antiviral herbal lip balm. The cytotoxic activities of C. laurifolius extracts and their ability to inhibit cytopathic effect were evaluated by colorimetric XTT test on Vero cells. In the first experiments, crude extracts did not show antiviral activity due to high toxicity. The solid phase extraction, purification, and polyphenolic enrichment methods were applied for EtOH, MeOH, and H2O extracts to reduce the toxicity of the extracts and in this way, high antiviral results were obtained. Polyphenol-enriched fractions of MeOH (SI 431.17) and H2O (SI > 455.37), purified with solid phase extraction, showed high antiviral effects against HSV-1. In vitro, cytotoxicity for polyphenol-enriched of EtOH, MeOH, and H2O from C. laurifolius was investigated on human dermal fibroblast cells to develop herbal lip balm formulations. All fractions had no cytotoxic effect on human dermal fibroblast cells. Herbal lip balm formulations were also developed, and evaluation tests were performed on the herbal lip balm in this study. Twenty-one different phenolic contents in the extracts were dereplicated by HPLC–DAD. The hyperoside (49.37 ± 0.53 mg/g extract), isoquercitrin (48.05 ± 0.74 mg/g extract), rutin (45.84 ± 1.02 mg/g extract), epicatechin (14.83 ± 1.00 mg/g extract), quercetin-3-O-glucopyranoside (13.35 ± 0.16 mg/g extract), catechin (12.80 ± 0.1 mg/g extract), caffeic acid (3.15 ± 0.18 mg/g extract), and apigenin (6.30 ± 0.10 mg/g extract) were determined as the major components present in the polyphenol-enriched fractions of C. laurifolius H2O extract. The results show that the polyphenol-enriched fractions of C. laurifolius extracts have good anti-Herpes simplex virus type-1 activity, and the herbal formulation with antiviral activity has a better option with minimum side effects. Graphical Abstract: (Figure presented.)