Abstract:A variety of sensing strategies in targeting biomarkers are emerging, as precise quantification of biomarkers can greatly reveal human health states and disease stages. However, when these biosensors are exposed to highly complex biological media, such as blood, serum, plasma, cell lysate and saliva, even diluted, their sensing interfaces suffer from serious biofouling, leading to an overwhelming background signal or biosensor malfunction. To address this problem, tremendous efforts have been devoted to construct antifouling sensing interfaces based on functional materials. Among the available antifouling materials, synthetic peptides have received increasing attention due to their flexibly tunable structures and naturally high biocompatibility that is beneficial for biosensor development. Nowadays, there are various reports about steady biosensing platforms based on antifouling peptides that are capable of assaying disease biomarkers in complex biological media. Herein, we concisely review, discuss and summarize recent advances in the construction of antifouling interfaces based on peptides, and their applications in target sensing in complex biological systems, especially blood-based fluids. Moreover, an outlook about opportunities and challenges of antifouling biosensing strategies that mainly based on functional peptides layers for biomarker assays is also presented.<br/> © 2020 Elsevier B.V.