OBJECTIVES: To assess whether the composition and charge of microemulsions affect their ability to simultaneously deliver α-tocopherol and lipoic acid into viable skin layers. METHODS: α-Tocopherol and lipoic acid were added (1.1 and 0.5% w/w, respectively) to decylglucoside-based microemulsions containing mono-dicaprylin. Microemulsions containing surfactant : oil : water (w/w/w) at 60 : 30 : 10 (ME-O) and 46 : 23 : 31 (ME-W), as well as a cationic form of ME-W containing 1% phytosphingosine (ME-Wphy) were characterized, and their ability to disrupt the skin barrier and deliver the antioxidants in vitro in the skin was evaluated. Antioxidant activity in ME-Wphy-treated skin was assessed using the thiobarbituric acid-reactive substances (TBARS) assay. KEY FINDINGS: The internal phase diameters of microemulsions ranged between 42 and 55 nm; phytosphingosine addition and pH adjustment to 5.0 increased zeta potential from -4.3 to +29.1 mV. ME-O displayed w/o structure, whereas ME-W and ME-Wphy were consistent with o/w. Microemulsions affected skin electrical resistance and transepidermal water loss, but did not affect lipoic acid penetration. α-Tocopherol delivery increased following the order ME-O < ME-W < ME-Wphy. ME-Wphy presented suitable short-term stability. The antioxidants delivered by ME-Wphy decreased TBARS cutaneous levels. CONCLUSIONS: Even though microemulsion structure only affected tocopherol penetration, delivered levels of both antioxidants were sufficient for a decrease in TBARS, supporting their use for enhanced protection.