To develop a wound dressing that can be removed from the injured skin without the damage and supporting rapid healing, we made hybrid dressing of small intestinal submucosa (SIS) and hydrogels. Alginate and gelatin used as a dressing material in hydrogels were selected to coat SIS sheets. Characteristics and tendency of wound healing of prepared sheets were investigated. Water uptake ability was greater when the sheets were coated with gelatin than alginate although both showed higher water absorption than the native SIS sheets, but the degradation rate of alginate/gelatin coated SIS was slower than that of native SIS because both polymers may delay contact time of enzyme to the SIS surface in solution. It was observed that less of fibroblasts attached to the natural polymer coated SIS sheets. This property will make easy for the detachment of the sheet from the defected tissue. Wound closure examination showed that prepared sheets enhanced wound healing. It was concluded that prepared alginate/gelatin coated SIS sheets are positively regarded as an appropriate biodegradable wound dressing that is reducing patient’s pain during change of the dressing.