<p>Poxvirus continues to pose public health concerns due to sporadic outbreaks, zoonotic transmission, and limited treatment options. The accessibility of vaccines and antivirals does not resolve the problems of drug resistance, adverse effects, and limited accessibility, which underscores the necessity to find different therapeutic approaches. This review aims to explore the potential of herbal therapy as an effective and accessible treatment for human poxvirus infections. A comprehensive analysis of 10 selected medicinal plants with reported antiviral activity against poxviruses. Data from in-vitro, in-vivo, in-silico, and clinical studies were analyzed to assess mechanisms of action, active compounds, and immunomodulatory effects. Plants such as <i>Azadirachta indica</i> (neem), <i>Curcuma longa</i> (turmeric), and <i>Echinacea purpurea</i> exhibit antiviral activity by inhibiting viral replication, modulating immune responses, and suppressing inflammation. Several herbs stopped viruses directly, and others supported the body’s natural defenses. Most evidence is preclinical, though some clinical data exist, particularly for <i>Echinacea</i>. Herbal remedies may provide new options for treating poxviruses and could help improve the effectiveness of available antiviral medication. However, more preclinical and clinical verification is necessary to show that the product is effective, safe, and appropriate for use. Integrating scientifically validated herbal therapies may provide cost-effective, accessible, and safer options for managing poxvirus infections, especially in low-resource settings.</p> Graphical abstract <p></p>