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Hydrogen/oxygen-generating biomaterials, a new trend in regenerative medicine, generate and supply hydrogen/oxygen to increase the local levels of hydrogen/oxygen to support tissue healing and regeneration. In this study, we carefully defined a strategic plan to develop a gas-permeable layer suitable for use in sanitary products that is capable of supplying hydrogen or oxygen in situ using calcium hydroxides as chemical oxygen sources. In vitro physicochemical evaluations of hydrogen- and oxygen-generation efficiency were performed to determine the amount of hydrogen and oxygen produced. An in vivo permeation study was conducted to assess biological parameters, including blood oxygen (O₂) and hydrogen (H⁺) levels. The stress hormone corticosterone and inflammation marker interleukin 6 (IL-6) were also quantified. The hydrogen/oxygen-generating patch (HOGP) continuously generated H⁺ or O₂ for up to 12 h after activation by water. An in vivo evaluation showed blood H⁺ peaked at 2 h after application of the HOGP and then progressively decreased until the end of study (24 h), whereas oxygen content (O2_(ct)) and oxygen saturation (SO2_(SAT)) continuously increased up to 6 h. Hematological and electrolyte parameters did not significantly change compared to baseline. Wearing the stretch fabric used to secure the patch did not significantly increase serum corticosterone or interleukin 6 (IL-6) in the animals. This novel design of a hydrogen/oxygen-generating biomaterial for supplying topical H⁺/O₂ may hold potential for increasing in situ or circulating H⁺/O₂ levels to improve healthcare outcomes. Full article