In this study, polysaccharide–richNymphaea hybridextracts (NHE) were obtained using the ultrasound-assisted cellulase extraction (UCE) method optimized by response surface methodology (RSM). The structural properties and thermal stability of NHE were characterized by Fourier-transform infrared (FT–IR), high–performance liquid chromatography (HPLC) and thermogravimetry–derivative thermogravimetry (TG–DTG) analysis, respectively. Moreover, the bioactivities of NHE, including the antioxidant, anti–inflammatory, whitening and scratch healing activities were evaluated by different in vitro assays. NHE conveyed a good ability to scavenge against the 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radicals and inhibit the hyaluronidase activity. NHE can effectively protect the HaCaT cells against oxidative damage by inhibiting the intracellular reactive oxygen species (ROS) production in the H2O2stimulation assays and promoting the proliferation and migration in the scratch assays. In addition, NHE was proven to inhibit melanin production in B16 cells. Collectively, the above results seem to be the evidence needed to promote the potential of NHE to be regarded as a new functional raw material in the cosmetics or food industries.