Background In many cases, human papillomavirus (HPV) infection is self‐limiting, as innate and adaptive cell‐mediated immunity is needed for infection elimination; however, the inability of the immune system in some patients to clear the infection is a matter of debate. The interleukin‐17 (IL‐17) family cytokines play an important protective role in host immune response to infections, through maintaining immunity against specific pathogens, induction of antimicrobial proteins, and recruitment of neutrophils to sites of invasion. Galectin‐3 (Gal‐3) may be considered as a marker of viral infection as many studies reported its increased serum level in viral infections. Aims To evaluate levels of serum Gal‐3 and IL‐17 in patients with verrucas and to explore the potential role of these markers in the pathogenesis of the disease. Methods Fifty patients suffering from HPV Infection, and fifty healthy controls were included in this study. Serum levels of Gal‐3 and IL‐17 were assessed using enzyme‐linked immunosorbent assay. Results The patients’ serum Gal‐3 was significantly higher, while IL‐17 was significantly lower than that of the healthy controls (p‐value < 0.001). Moreover, a statistically significant positive correlation was found between Gal‐3 serum level and disease duration and number of warts. Significant negative correlation exists between IL‐17 and Gal‐3 levels. Conclusion Our results indicate a potential role of both IL‐17 and Gal‐3 in the pathogenesis of warts and open a new opportunity in targeting these markers in the future in treating warts.