Excessive UV irradiation induces photoaging and overproduction of melanin, which darkens the skin and affects appearance. To efficiently enhance transdermal delivery and anti-pigmentation, a novel ROS-responsive transdermal nanocarrier for the whitening agent Glabridin by integrating the cell-penetrating peptide polyarginine R8 and borate ester bond into hollow mesoporous silica nanoparticles (HMSNs) has been designed, in which beta-cyclodextrin (β-CD) was grafted onto the surfaces of HMSNs via boronic ester bond to avoid premature release of Glabridin, and R8 conjugated adamantane (Ada) was anchored on HMSN-β-CD via host-gust interaction to enhance the drug delivery efficiency. The ROS-responsive HMSN-β-CD/Ada-R8 nanocarrier was characterized by TEM, FTIR, TGA, Zeta potential, N2 adsorption, stability, and other parameters. The nanocarrier rapidly penetrated through the epidermis into the keratinocytes and melanocytes and released Glabridin in a controlled ROS-responsive manner. Glabridin released from nanocarriers reversed UV-induced oxidative damage and phototoxicity and reduced hyperpigmentation. Taken together, our study provides a guidance for the design and fabrication of functional transdermal drug nanocarriers for cosmetic applications.