Hypericum perforatum oil (HPO) was known as Saint John's wort oil which has antibacterial properties for medicinal applications. (topically to heal wounds). In this study, Pickering sponges containing HPO have been stabilized using β-cyclodextrin (β-CD) natural substance while Polyvinyl alcohol/sodium carboxymethyl cellulose (PVA/CMC) polymer matrices. The β-CD/HPO inclusion complexes were added to the PVA/CMC sponges in various ratios (1 : 1, 1 : 4, and 1 : 8) and morphological, thermal and physical properties of sponges were investigated based on the ratios. SEM images revealed all Pickering PVA/CMC/HPO sponges has good porosity and PVA/CMC sponges containing (1 : 8 w/v) of β-CD/HPO indicated the highest porosity. Furthermore, existence of HPO in the sponges were confirmed by FT-IR analysis. Similarly, thermal stability is increased as the β-CD/HPO increased. Contact angle value rise from 12.7°to 89.9°as HPO concentration increased, and this value is the ideal hydrophobicity for the skin. Antibacterial efficiency showed good antibacterial activities of Pickering sponges containing the highest amount of HPO (1 : 8 w/v of β-CD/HPO) against Gram (À ) (Escherichia coli), and Gram (+) (Staphylococcus aureus, P. aeruginosa) bacteria with 13-17 mm zone inhibition diameter. All samples showed biocompatibility, and the material with the lowest amount of HPO (1 : 1 w/v of β-CD/HPO) having the best biocompatibility. The increase in the HPO amount in Pickering sponges caused a decrease in mechanical properties. As a result, the resulting PVA/CMC/HPO Pickering sponges can be utilized in wound dressing applications owing to their imroved antibacterial activity results.