Peri-implant disease is not merely a local condition. As a chronic inflammatory focus, it may exert systemic effects on overall health. As key systemic inflammatory markers, serum CRP and IL-6 provide direct evidence for revealing the association between peri-implant diseases and systemic health. This review aims to systematically evaluate the existing evidence on the correlation between serum CRP, IL-6 and peri-implant disease, explore their connection and related mechanisms with peri-implant disease, and discuss the potential clinical implications and future research directions in disease risk assessment, therapeutic effect monitoring and systemic health management.