The abilities of water and ethanol extracts of Opuntia humifusa cladode powder to protect against atopic dermatitis in NC/Nga mice were investigated for application of O. humifusa cladodes as functional food materials. Water extract-treated group (OHW) and ethanol extracttreated group (OHE) mice exhibited protective effects against skin lesions, such as reduced hemorrhaging and epidermolysis. The number of mast cells in skin tissues of OHE group mice was 9.3±2.7 units, which was significantly (p<0.05) decreased compared with other group mice. The serum level of IgE in OHE group mice (1,156±35.19 ng/ mL) was significantly (p<0.05) decreased, compared with other group mice. The serum histamine concentrations in OHW and OHE groups mice were significantly (p<0.05) decreased, compared with control group mice. Overall, 75% ethanol extracts provided greater protection than water extracts. O. humifusa cladode extracts have potential for future use as functional materials.