The purpose of this study was to investigate the anti-aging, anti-bacterial, and anti-inflammatory effects of a hot water extract of Duchesnea indica (DIW). The anti-aging properties of this extract were assessed as anti-elastase, 1,1-diphenyl-2-picrylhydrazyl (DPPH) scavenging, 2,2-azinobis 3-ethylbenzothiazoline-6-sulfonic acid (ABTS) scavenging, and pigmentation activities. We also investigated the anti-inflammatory potential of DIW in lipopolysaccharide-stimulated RAW 264.7 macrophage cells. DIW possessed high elastase inhibitory, and DPPH and ABTS radical scavenging activities (IC50s; 35.1, 19.2, and 84.0 μg/mL, respectively). We determined the antibacterial activities of DIW using minimum inhibitory concentration (MIC) values. DIW showed excellent antibacterial activities against drug-susceptible and -resistant skin pathogens such as Propioni bacterium acnes, Staphylococcus epidermidis, and Staphylococcus aureus, with MICs ranging from 78.1 to 1250 μg/mL. DIW significantly stimulated melanin synthesis of B16 mouse melanoma cells, and inhibited nitric oxide synthesis of RAW 264.7 macrophage cells, in a concentration-dependent manner. DIW also effectively attenuated expression of the inflammation-mediating enzyme, inducible nitric oxide synthase, at the protein level in a concentration-dependent manner. The high-performance liquid chromatography fingerprint of DIW indicated the presence of quercetin and kaempferol at 25.3 and 12.0 μg/mL, respectively. To evaluate the safety of DIW, the human skin primary irritation test was performed on normal skin (upper back) of 31 volunteers to determine if any constituent presented an irritation or sensitization potential. DIW did not induce any adverse reactions at 100 μg/mL. Taken together, our results suggest that DIW may be considered as an anti-aging and anti-inflammatory candidate for cosmeceutical applications.