β-Amyloid1-42, the major constituent of amyloid plaques, was believed to play a central role in the neuropathology of AD according to the ‘‘amyloid cascade hypothesis''. In our study, we evaluated the in vitro profiles of four Roselle extracts against Aβ42 production. The in-vitro Aβ42 inhibiting activity was evaluated in a human neuroglioma cell line (H4) carrying the double Swedish mutation (K670N/M671L) of the human amyloid precursor protein (APPsw) under the transcriptional control of the hamster prion protein promoter. The in-vitro anti-COX activity was also investigated using human recombinant enzymes isolated from transfected Sf-9 cells. In addition, the cytotoxicity study by standard MTT assay and the antioxidant activity of Roselle extracts using DPPH Free Radical Scavenging Assay was also investigated. All Extracts concentrations showed a good inhibitory activity against DPPH free radical. The antioxidant activity of our extracts as IC50 was in the range of (45.5 - 88.5 µg/ml) among the four Roselle extracts within the two solvent system compared to 47.5 µg/ml of Gallic acid. No toxicity was detected by standard MTT assay against H4 cells treated with Roselle extracts by concentrations up to 600 ng/ml. A dose dependent inhibition of Aβ42 secretion was observed. Our Roselle extracts were found to be 1.5- and 3-fold more potent than R-flurbiprofen in inhibiting Aβ42 secretion and able to modulate the in vitro Aβ42 secretion without any cytotoxic effect. No inhibition activity was also observed against COX-1 and COX-2 up to 600 ng/ml concentration indicating that the reduction in Aβ42 levels may be independent of COX activity.