The design and synthesis of hybrid molecules encompassing two pharmacophores in one molecular scaffold is a well-established approach to the synthesis of more potent drugs with dual activity. In this chapter, we will present the most important synthetic methodologies we have applied for the preparation of hybrid compounds containing the “universal antioxidant” α -lipoic acid. Experimental details for the synthesis and purification techniques of specific examples of molecules will be given. The synthesized molecules combine antioxidant activity with a variety of other biological activities such as protection against reperfusion arrhythmias, neuroprotective, and anti-inflammatory activity.