Bacterial infections of biofilms are hard to treat as the matrix and physiological differences in the cells within a biofilm limit the ability of traditional antibiotics to control the growth of bacteria. We synthesized a sodium butyrate-encapsulated manganese tetrakis (4-carboxyphenyl) porphyrin hydrogen-bonded organic framework (NaB@Mn-TCPP HOF), which was used to determine its physical and chemical properties, guest-loading capacity, release behavior, hemolytic effects, antibacterial activity and anti-biofilm formation of Escherichia coli and Staphylococcus aureus. The NaB incorporation was confirmed by Fourier-transform infrared spectroscopy, powder X-ray diffraction, ultraviolet-visible spectroscopy, dynamic light scattering, zeta-potential measurement, elemental mapping, and other methods demonstrated that the parent Mn-TCPP HOF retained most of its principal spectroscopic, solid-state diffraction, and colloidal features. Indirect spectrophotometry of absorbance of UV light revealed an apparent loading of NaB of 56 percent with respect to the mass of carrier at feed ratio of 4 mg NaB per 5 mg carrier corresponding to an estimated NaB content of about 36 wt% in the recovered composite and an apparent encapsulation rate of about 70%. About half of the calculated loaded NaB was released gradually over 12 h without reaching the final plateau. In a five-group design that is exploratory and not dose-matched, images of the colonies were taken after exposure to 660 nm irradiation at 100 mW cm−2, and the results indicated the reduction of colony development, crystal-violet staining, propidium-iodide-associated signal, and surface-related bacterial coverage in the NaB@Mn-TCPP HOF group. Biofilm experiment was performed on the inhibition of a new biofilm in the course of 24 h instead of destroying an already matured one. After 2 hours of exposure, less than 5 percent hemolysis was produced by the composite at 100 micrograms mL −1. These findings can be used to make further studies of NaB@Mn-TCPP HOF as a combined material platform that reacts to light. It has not been clarified by the current design whether reactive oxygen species, manganese excretion, the pathway of bacteria controlled by NaB, or pharmacological interactions were involved.