Background The “all-on-four” concept represents a significant advancement in dental implantology. particularly beneficial in cases of extensive jaw bone loss where invasive bone regeneration procedures are typically required. However, the successful implementation of this technique necessitates meticulous planning concerning implant selection, materials, and prosthesis design. The recent introduction of PEEK (Polyetheretherketone) in dentistry, especially in all-on-four prosthetics, prompts questions regarding its clinical efficacy and comparative biomechanical and biological advantages over conventional materials such as titanium and zirconia. While some studies have compared PEEK with other materials, systematic reviews evaluating its efficacy are scarce. This systematic review protocol intends to assess the evidence regarding the viability of PEEK as a potential alternative within the all-on-four approach in dental implantology. Methods This systematic review protocol will adhere to the Cochrane Handbook for Systematic Review of Interventions and align with the Methodological Expectations of the Cochrane Intervention Reviews (MECIR) guidelines. Utilizing a comprehensive search strategy, multiple databases, including PubMed, EMBASE, Scopus, EBSCO, Web of Science, Cochrane Central, and registries of clinical trials, will be explored. The search aims to identify randomized controlled trials and non-randomized studies investigating the application of PEEK in the all-on-four approach for dental procedures. Emphasizing clinically relevant outcomes such as implant survival, prosthesis success, peri-implant complications, and patient satisfaction, this review aims to provide insights into the effectiveness and potential benefits of using PEEK in all-on-four prosthetics. Non-randomized studies will be assessed for bias using ROBINS-I, while randomized controlled trials will undergo evaluation with the Cochrane Risk of Bias assessment tool, ROB II. Discussion The outcomes derived from this systematic review hold great significance for dental practitioners exploring the all-on-four concept. Understanding PEEK’s advantages and limitations compared to titanium and zirconia facilitates tailored treatment plans, enhancing success and satisfaction, ultimately improving dental care quality. Systematic review registration PROSPERO: CRD42024531175 (Registered on 13/04/2024).