The objective of this study was to perform a structural characterization and evaluate the in vitro safety profile and in vitro antioxidant activity of liquid crystalline systems (LCS) with and without retinyl palmitate (RP). LCS containing polyether functional siloxane (PFS) as a surfactant, silicon glycol copolymer (SGC) as oil phase, and water in the ratios 30 : 25 : 45 and 40 : 50 : 10 with (OLS(v) = RP-loaded opaque liquid system and TLS(v) = RP-loaded transparent liquid system, respectively) and without (OLS and TLS, respectively) RP were studied. Samples were characterized using polarized light microscopy (PLM) and rheology analysis. In vitro safety profile was evaluated using red cell hemolysis and in vitro cytotoxicity assays. In vitro antioxidant activity was performed by the DPPH method. PLM analysis showed the presence of lamellar LCS just to TLS. Regardless of the presence of RP, the rheological studies showed the pseudoplastic behavior of the formulations. The results showed that the incorporation of RP in LCS improved the safety profile of the drug. In vitro antioxidant activity suggests that LCS presented a higher capacity to maintain the antioxidant activity of RP. PFS-based systems may be a promising platform for RP topical application for the treatment of skin aging.