Malassezia is a genus of commensal and lipid-dependent yeasts in human skin which also have a pathogenic lifestyle associated with several common skin disorders such as atopic dermatitis and eczema. Symptoms include red, itchy, and inflamed skin. We studied the growth characteristics and biochemical analyses of M. furfur which showed that the protein contents were greater in extracts taken at 24 h. These were then used to infect C57BL/6 mice, resulting in skin rupture. Polygalaxanthone III (POL), a more effective anti-inflammatory ingredient in Polygala japonica Houtt., was applied externally to the ulceration and successfully healed the wounds quickly. POL could not inhibit Malassezia activity as tested by the inhibition zone test, but affected the formation of lipid droplets in HaCaT cells. The wound-healing molecular mechanisms may be involved in the STAT3 pathway according to the Western blot results of skin tissues. Malassezia’s role in skin health is far from certain, and there is no clear solution, so understanding the development of Malassezia-associated skin diseases in general and seeking solutions are very important.