A micro-nanostructure-based surface-modified fiber-optic sensor has been developed herein to selectively detect hydrogen peroxide (H2O2). In our design, phenylboronic ester-modified polymers were used as a modified cladding medium that allows chemo-optic transduction. Sensing is mechanistically based on oxidation and subsequent hydrolysis of the phenylboronic ester-modified polymer, which modulates hydrophobic properties of fiber-optic devices, which was confirmed during characterization of the chemical functional group and hydrophobicity of the active sensing material. This work illustrates a useful strategy of exploiting principles of chemical modifications to design surface-wettable fiber-optic sensing devices for detecting reactive species of broad relevance to biological and environmental analyses.