Sulfated phenolic polymers have extensively been investigated as anticoagulant agents in view of their higher bioavailability and resistance to degradation compared to heparins, allowing for increased half-lives. In this frame, we report herein the preparation of sulfated derivatives of tyrosol, one of the most representative phenolic constituents of extra virgin olive oil, by different approaches. Mild sulfation of OligoTyr, a mixture of tyrosol oligomers, that has been reported to possess antioxidant properties and osteogenic activity, afforded OligoTyrS I in good yields. Elemental analysis, NMR, and MALDI-MS investigation provided evidence for an almost complete sulfation at the OH on the phenylethyl chain, leaving the phenolic OH free. Peroxidase/H2O2 oxidation of tyrosol sulfated at the alcoholic group (TyrS) also provided sulfated tyrosol oligomers (OligoTyrS II) that showed on structural analysis highly varied structural features arising likely from the addition of oxygen, derived from water or hydrogen peroxide, to the intermediate quinone methides and substantial involvement of the phenolic OH group in the oligomerization. In line with these characteristics, OligoTyrS I proved to be more active than OligoTyrS II as antioxidant in the 2,2-diphenyl-1-picrylhydrazyl (DPPH) and ferric reducing/antioxidant power (FRAP) assays and as anticoagulant in the classical clotting times, mainly in prolonging the activated partial thromboplastin time (APTT). After intraperitoneal administration in mice, OligoTyrS I was also able to significantly decrease the weight of an induced thrombus. Data from chromogenic coagulation assays showed that the anticoagulant effect of OligoTyrS I was not dependent on antithrombin or factor Xa and thrombin direct inhibition. These results clearly highlight how some structural facets of even closely related phenol polymers may be critical in dictating the anticoagulant activity, providing the key for the rationale design of active synthetic nonsaccharidic anticoagulant agents alternative to heparin.