Purpose <p>This study aimed to develop, by the solvent casting method, poly(vinyl alcohol) (PVA) and hydroxypropyl methylcellulose (HPMC E4M)-based patches for periorbital hyperpigmentation incorporating açaí oil (<i>Euterpe oleracea</i>), barbatimão glycolic extract (<i>Stryphnodendron</i> spp.), and hyaluronic acid, and to evaluate preliminarily their cytotoxicity and ex vivo skin hydration potential using in vitro and ex vivo screening models.</p> Methods <p>Patches were prepared using two drying methods: oven-drying (40&#xa0;°C for 20&#xa0;h) or lyophilization (24&#xa0;h). Structural stability after hydration was assessed. Cytotoxicity was evaluated using the XTT assay in RPE-1 hTERT TP53KO cells, considered a suitable in vitro model for early-stage safety evaluation. Ex vivo hydration potential was measured on porcine ears using a portable bioelectrical impedance device.</p> Results <p>Lyophilized patches exhibited uniform shape with balanced softness and flexibility. Base and hyaluronic acid-containing patches were nontoxic, maintaining normal cell morphology and viability, whereas açaí oil or barbatimão extract induced cytotoxic effects. The hyaluronic acid-containing patch increased water content in porcine skin in a time-dependent manner, and maintained higher values of water content from 15 to 120&#xa0;min.</p> Conclusion <p>PVA and HPMC E4M-based patches were successfully prepared with 24&#xa0;h of lyophilization. Hyaluronic acid-containing patch showed in vitro preliminary safety and ex vivo skin hydration promoting potential. Cytotoxicity of açaí oil and barbatimão extract highlights the need for further experiments in models that better recapitulate periocular skin complexity. Additional studies using hydration measurement methods using validated equipment and in vivo human models are required to confirm efficacy and safety for periocular applications.</p>