Crabs, decapods crustaceans, have been recognized as a rich natural source of unique antioxidant and therapeutic agents. Callinectes sapidus is an edible crab used as a popular food source in coastal cities like Port Said, Egypt. In the present study, in vitro  cytotoxic and antioxidant properties of the hepatopancreas and hemolymph of C. sapidus were investigated on some human cell lines (HeLa, HepG 2, MCF-7,  MDA-MB-231 and  WI-38). The MTT results showed that both extracts possess selective cytotoxicity against HepG2, MCF-7 and HeLa. No cytotoxicity was observed on normal lung cells (WI-38). The hepatopancreas and hemolymph showed the highest antiproliferative activity against HeLa cells (IC₅₀: 0.39 and 2.01 mg/ml respectively). Flow cytometry revealed that both extracts can induce apoptosis in HeLa cells and cause cell cycle arrest in the G2/M phase after 48 h treatment.  Hepatopancreas showed greater DPPH radical-scavenging activity with IC₅₀ value of 38.99 µg/ml than hemolymph (IC₅₀ value of 464 µg/ml). Both extracts at 2 mg/ml were effective to attenuate the perturbations in the tested parameters (superoxide dismutase, catalase, reduced glutathione and malondialdehyde) of H₂O₂-induced oxidative stress in WI-38 cells. Findings suggest that these blue crab extracts have protective effects on H₂O₂-induced lipid peroxidation and might be used for the development of new drugs against human cervical adenocarcinoma.