The antioxidant activity (oxygen radical absorbance capacity, ORAC) and total phenols and flavonoids were determined in extracts from digestive tract, gonads, muscles and respiratory apparatus of sea cucumber, Cucumaria frondosa. Total phenols content varied from 22.5 to 236.0 mg of gallic acid equivalents/100 g dw, and flavonoids from 2.9 to 59.8 mg of rutin equivalents/100 g. ORAC values ranged from 140 to 800 μmol of Trolox equivalents/g dw. Among all extracts, best antioxidant potencies were observed in ethyl acetate extracts from digestive tract, and in acetonitrile-rich fractions obtained from mixed extracts using acetonitrile/TFA (trifluoroacetic acid) acidified water on muscles, gonads and respiratory apparatus. The weakest potencies were observed with water extracts from digestive tract and respiratory apparatus, and with water-rich fractions obtained from mixed extraction of gonads and muscles. A significant correlation was observed between ORAC values and total phenol content in extracts and fractions of gonads and muscles, but ORAC and phenols were not correlated in digestive tract and respiratory apparatus extracts. ORAC values were significantly correlated (p < 0.05) with total flavonoids in all extracts. Successive eluates obtained from solid-phase extraction of water-rich fractions using C18 cartridge showed ORAC values (105–500 μmol of TE/g) reaching up to 2.3 times the potency of their parent fractions. Flavonoids are suggested to be mainly responsible for observed activities. Our results provide a first quantitative evaluation of C. frondosa tissues as useful sources of antioxidants for human consumption.