The involvement of oxidative stress in the aetiology of various multifactorial diseases is well known, just as the design of multifunctional compounds is recognized as an innovative strategy to control complex-spectrum diseases. The purpose of this work was to synthesize a small library of six benzothiazole derivatives with hydrazonic spacers and to evaluate their multifunctional efficacy in terms of antioxidant, UV-filtering, antiproliferative, and anti-inflammatory activities. From the SAR study it emerged that the hydrazone linker, when coupled with a hydroxyl group in position 4 and another hydroxyl or methoxyl in position 3, seems to direct the profile of the molecule towards multifunctionality. The antitumor activity against melanoma cells seems to be related to the inhibition of tyrosinase (BZTidr10–12). All the compounds of the series have shown to be direct inhibitors of 5-lipoxygenase (5-LO). In particular, compound BZTidr12, with an IC₅₀ of 0.03 µM, proved to be the most potent inhibitor of the series against isolated 5-LO activity in a cell-free assay.