The human skin is pivotal for protecting the body from various stresses and diseases, regulating several physiological aspects, and sensing any signal changes around the environment. To work and function optimally, the skin should be protected and cared regularly by using some treatments. Chalcone, as a privileged structure, exhibits wide and unique bioactivities related to several skin disorders such as in preventing and treating pigmentation disorders (melasma and vitiligo), cutaneous leishmaniasis, rashes (acne vulgaris, seborrheic dermatitis and dandruff, psoriasis and atopic dermatitis), and rosacea. In this chapter, the role of chalcone derivatives in treating several skin disorders as mentioned above is discussed to provide a brief and comprehensive perspective regarding the role of chalcone in dermatology including in vitro, preclinical, and clinical assays.