Introduction: At present, acyclovir is commercially available as the drug of choice for managing herpes simplex type I (HSV-1) viral infection. However, the high prevalence of the infection coupled with the emergence of resistant viral strains has limited its effectiveness. Thus, the development of novel antiviral agents is crucial. Practitioners of herbal medicine in Kenya make use of Dicrocephala integrifolia (DI) for the management of several diseases including viral infections. However, information on the efficacy of this plant against HSV-1 viral infection is not available. The aim of the present study was to determine the in vitro antiviral activity of crude extracts of DI against HSV-1. Methods: Leaves, roots, flowers and stems of DI were extracted using water (W) and methanol (ME) and qualitatively screened to identify the phytoconstituents present. Furthermore, the anti HSV-1 activity of the obtained extracts was evaluated on Vero cell lines using the 3-[4, 5 dimethylthiazol-2-yl]-2, 5-diphenyltetrazolium bromide] assay. The 50% cytotoxic concentration (CC 50 ) and 50% effective concentration (EC 50 ) of each extract was determined using regression analysis. The effects of crude DI extracts on adsorption and post-adsorption stages of the HSV-1 replication cycle was evaluated against acyclovir using a cytopathogenic inhibition assay. Results: Alkaloids, glycosides, flavonoids, phenols, saponins, tannins and terpenoids were found to be present in the extracts. The CC 50 values of the aqueous DI extracts was in the range 71.31 ± 2.65 to >100 µg/ml compared to >100 µg/ml of acyclovir. The EC 50 values of crude extracts of DI on the pre-adsorptive phase of HSV-1 activity was in the range 54.45±3.45 to >100µg/ml compared to 4.772±7.81µg/ml of acyclovir whilst the EC 50 value of the crude extracts of DI on the post-adsorptive phase of HSV-1 activity was in the range 45.270±4.31 to >100µg/ml compared to >100µg/ml of acyclovir. Conclusion: The results suggest that crude extracts of DI may be a reservoir of phytochemicals with potentially good efficacy against HSV-1.