The interleukin-17 signaling pathway plays a critical role in the pathogenesis of psoriasis. By inhibiting this pathway, there is a reduction in the severity of psoriasis and many patients achieve clear skin. We present two individuals, a 34-year-old male and a 40-year-old female, who developed aphthous ulcers on the oral mucosa and oral and vulvar mucosa, respectively, while undergoing treatment with interleukin-17 inhibitors. The ulcers did not respond to conventional therapy, including topical corticosteroids and nystatin 100,000 unit/mL oral suspension. Both patients underwent biopsies which confirmed the diagnosis of ulcer. Once confirmed, the interleukin-17 inhibitor was discontinued and the ulcers resolved in both cases. As we see biologic treatment, specifically interleukin-17 inhibitor, becoming more popular for the treatment of psoriasis, it is important for physicians to be aware of this potential adverse event. Early detection and intervention are important to avoid complications that can develop from rare but often painful ulcers.