Herbal products have steadily gained popularity as alternatives to conventional, synthetic medications and are sought after by patients for the treatment of chronic dermatologic diseases and for cosmeceutical use. The production and distribution of botanical extracts is largely unregulated and therefore extensive research into their mechanism of action, safety, physiologic stability, and optimal dosing has been overlooked. One of the major pathways through which natural supplements, particularly polyphenols, act is via inhibition of oxidative stress and its downstream mediators. Endogenous defense mechanisms are inadequate to combat oxidative stress and therefore dietary and/or topical supplementation with polyphenols are an important complementary preventative and therapeutic strategy. This review focuses on the molecular targets of common polyphenols used in topical preparations, particularly soy, green tea, oats, curcumin, and silymarin. Continued research into bioavailability and function of these agents will help translate their therapeutic potential to treat clinical disease.