In this study, we investigated the antimicrobial, antioxidant, and cytoprotective activities of ethanol extract and the ethyl acetate (EtOAc) fraction of P. kleiniana Wight & Arn. The EtOAc fraction exhibited antimicrobial effects against most of the microorganisms that were tested, including Staphylococcus aureus, Candida albicans, Pseudomonas aeruginosa, and, Escherichia coli, but not Aspergillus niger. In addition to its excellent antioxidant activity, the EtOAc fraction attenuated the UVB-induced cell death via upregulation of caspase-3 expression in human keratinocytes. The HPLC/ESI-MS/MS analysis allowed identification of the components in the EtOAc fraction. Overall, our results suggest that P. kleiniana is a valuable source of bioactive compounds for the development of pharmaceuticals and cosmetics.