ABSTRACT Purpose Non-melanoma skin cancers (NMSCs) of the periocular region present significant clinical challenges, with basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) being the most prevalent. The purpose of this study is to report on the outcomes of anti-programmed death (PD-1)/PD-L1 immunotherapy in patients with locally advanced periorbital NMSCs. Methods We conducted a retrospective study of the patients treated for locally advanced periocular BCC and cutaneous SCC using anti-PD-1/PD-L1 immunotherapy from January 2016 to January 2023. Patient records were reviewed for clinical and histological data, and all were evaluated for the effectiveness of the therapy. Results The study included nine patients with a mean age of 68.2 years. Four patients had periocular BCC, and five had cutaneous SCC. Most patients had received prior treatments, including surgical resection, radiation, and systemic chemotherapy. Six patients were treated with cemiplimab, one with nivolumab, one with pembrolizumab, and one underwent trials of all three medications. Anti-PD-1/PD-L1 therapy proved effective in two patients with BCC and two with SCC. All responsive cases were treated with cemiplimab. Conclusion Anti-PD-1/PD-L1 immunotherapy appears to be a promising option for treating locally advanced periocular BCC and cutaneous SCC, especially in cases where traditional treatments fail. Future research should involve nationwide databases or multi-institutional collaborations to validate the results and clarify the use of immune checkpoint inhibitors for periorbital NMSCs as adjuvant therapy.