Phytochemical investigation of the whole plant of Lepisorus contortus(Christ) Ching led to the isolation of five new phenylethanoid glycosides (1−5), each containing a caffeoyl group, a new flavonoid glycoside (10), and 14 known compounds (6−9and 11−15, syringic acid, vanillic acid, phloretic acid, diplopterol, and β-sitosterol). This is the first report of phenylethanoid glycosides from the family Polypodiaceae. Compounds 1−15were evaluated for their cancer chemopreventive potential based on their ability to inhibit tumor necrosis factor alpha (TNF-α)-induced NF-κB activity, nitric oxide (NO) production, and aromatase, quinone reductase 2 (QR-2), and COX-1/-2 activities. Quercetin-3-O-β-d-glucoside (15) demonstrated inhibition against QR2 with an IC50value of 3.84 μM, which confirmed kaempferol/quercetin glycosides as the active compounds to inhibit QR2. The compound also demonstrated NF-κB activity with an IC50value of 33.6 μM. In addition, compounds 1, 2, 4, and 6showed aromatase activity with IC50values of 30.7, 32.3, 26.8, and 35.3 μM, respectively.