Carbon fiber-reinforced polyetheretherketone (CFR-PEEK) as an alternative to metallics in orthopedic implants offers biomechanical and radiological advantages. However, the extent of wear particle generation and its clinical impact are unclear. This systematic review evaluates clinical evidence of wear in fracture fixation devices. A systematic search was conducted to identify clinical studies reporting wear of metallic and CFR-PEEK implants used in extremities. Nineteen studies were included: three prospective cohorts, eight retrospective cohorts, one case series, and six case reports. Among 208 fixation plates, 43 were CFR-PEEK and all 93 intramedullary nails were metallic. Risk of bias ranged from low to serious, mainly due to selection bias. Wear-related complications were reported for both materials. Metallic implants showed elevated serum ion levels, metallic debris in tissues, and, in some cases, metallosis. CFR-PEEK implants showed limited evidence of carbon fiber fragments near implants. One comparative study reported higher inflammatory responses in CFR-PEEK explants, though no direct link between debris and implant removal was found. Both metallic and CFR-PEEK fracture fixation devices generate wear particles, which may induce biological responses. However, wear-related complications appear rare, especially with validated implant designs, and clinical significance of wear debris remains limited.