We report the development of a type of novel hybrid photosensitizers for photodynamic inactivation of broad-spectrum bacteria. A thiol-modified amphiphilic block copolymer, poly(N-isopropylacrylamide-block-styrene), was synthesized and characterized. Subsequently, silver nanoparticles stabilized by poly(N-isopropylacrylamide-block-styrene) were synthesized and used to entrap hydrophobic photosensitizing molecules (such as hematoporphyrin). The resulting water-dispersible hybrid photosensitizers demonstrated enhanced singlet oxygen generation with a broadened excitation profile, as compared to the pristine hematoporphyrin molecules. Photodynamic inactivation of Staphylococcus epidermidis and Escherichia coli by the hybrid photosensitizer showed significantly enhanced killing efficacy, up to ∼5 orders of magnitude, under both white light and red/near-infrared light illuminations. The hybrid photosensitizers at the concentration used in the photodynamic inactivation assays displayed low cytotoxicity to Hela cells under ambient light conditions. These results demonstrate the great potential of such hybrid photosensitizers for photodynamic inactivation and photodynamic therapy applications.