The aim of this research was to investigate the antioxidant and anti-apoptotic activities of Potentilla anserina polysaccharide (PAP) on kidney damage induced by cadmium (Cd) in vitro and in vivo. PAP has been suggested to have anti-oxidation, anti-apoptosis, immunoregulation, antimicrobial, antitussive, and expectorant abilities. In this study, PAP was extracted and the major components of PAP were analyzed. It was shown that PAP pretreatment remarkably improved redox homeostasis, both in human embryonic kidney 293 (HEK293) cells and in BALB/c mice. Administration of PAP attenuated the mitochondrial dysfunction, degeneration, and fibrosis of kidney induced by Cd. Furthermore, PAP exhibited anti-apoptotic activity, which involved regulating both the mitochondria-mediated intrinsic apoptotic pathway and the death receptor-initiated extrinsic pathway. These results suggest that PAP is a potential therapeutic agent for Cd-induced nephrotoxicity.