Palmoplantar pustulosis (PPP) is a chronic inflammatory disease involving the palms and soles, and characterized by sterile pustules. Conventional treatments are often ineffective, and guselkumab, an IL-23 inhibitor, is the only approved biologic agent for treating PPP in South Korea and Japan. However, there is no report analyzing the real-world outcomes in South Korea. In our retrospective study, half of the six newly diagnosed patients showed a 50% or greater reduction in the Palmoplantar Pustulosis Area and Severity Index before 20 weeks of guselkumab treatment, while the remaining patients achieved this improvement only by week 28. One patient maintained a significant effect even at 100 weeks of treatment. All patients experienced improvement in their dermatology life quality index, particularly those with nail abnormalities. Unlike its efficacy in psoriasis treatment, guselkumab showed a delayed response when used for PPP, highlighting the need to consider this factor in evaluating its clinical effectiveness.