Eczematous paradoxical reactions are commonly associated with anti-interleukin-17A (anti-IL-17A) antibodies. However, IL-23 p19 inhibitors can also cause similar cutaneous manifestations. We present a case of a 77-year-old Japanese woman with palmoplantar pustulosis (PPP), who developed eczematous lesions on her face, neck, and dorsum of the hands 10 weeks after initiating guselkumab treatment. Patch tests revealed a positive reaction to flowers and leaves, confirming a diagnosis of contact dermatitis. This was notable, as the patient had routine contact with every morning for years without prior allergic reactions, until after initiating anti-IL-23 p19 antibody treatment. Given the temporal association and potential causal link with guselkumab administration, the treatment was discontinued, and avoiding contact with the plant improved the contact dermatitis eruptions. Concurrently, PPP lesions remained unchanged. IL-23 inhibition is known to skew the IL-12/T-helper 1 (Th1) axis, resulting in increased interferon-γ (IFN-γ) production, a cytokine implicated in the early sensitization phase of allergic contact dermatitis (ACD). Despite prior tolerance, this case report highlights the importance of considering drug-induced ACD in patients presenting with new-onset eczema while on biologic therapy, particularly in susceptible individuals.