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Plant polyphenols possess diverse bioactivities, including antiviral activity against a broad spectrum of viruses. Here, we investigated the virucidal properties of an <i>Kalanchoe daigremontiana</i> extract using an in vitro model of human herpesvirus type 1 (HHV-1) infection. Chromatographic analysis indicated that the extract of <i>Kalanchoe daigremontiana</i> is rich in various compounds, among which are polyphenols with virucidal activity confirmed in the literature. We found that <i>Kalanchoe daigremontiana</i> extract shows an ability to prevent HHV-1 infection by direct inhibition of the virus attachment, penetration, and blocking of infection when used in pretreatment or post-entry treatment. Our results indicate that <i>Kalanchoe daigremontiana</i> extract may be a good candidate drug against HHV-1, both as a substance to prevent infection and to treat an already ongoing infection. Our findings illustrate that <i>Kalanchoe daigremontiana</i> could be a potential new candidate for clinical consideration in the treatment of HHV-1 infection alone or in combination with other therapeutics.