This study aims to validate a new cosmetic ingredient from Salicornia ramosissima S J. Woods through in vitro and ex vivo assays. The halophyte extracts were obtained by subcritical water extraction (SWE) at different temperatures (110, 120, 140, 160 and 180 °C). The antioxidant/radical scavenging activities and the phenolic profile were screened for all extracts. The optimal extract was assessed in keratinocytes and fibroblasts, while permeation assays were performed in Franz cells. The inhibitory activity of hyaluronidase and elastase was also evaluated. The sample extracted at 180 °C presented the highest phenolic content (1739.28 mg/100 g of dry weight (dw)). Despite not being efficient in the sequestration of ABTS^•+, this extract scavenged the DPPH^• (IC₅₀ = 824.57 µg/mL). The scavenging capacity of superoxide (O₂^•−) and hypochlorous acid (HOCl) was also considerable (respectively, IC₅₀ = 158.87 µg/mL and IC₅₀ = 5.80 µg/mL). The cell viability assays confirmed the absence of negative effects on keratinocytes, while the fibroblasts’ viability slightly decreased. The ex vivo permeation of rutin, quercetin and syringic acid after 24 h was, respectively, 11, 20 and 11%. Additionally, the extract showed a good elastase and hyaluronidase inhibitory activity. The results obtained support the S. ramosissima bioactivity as a cosmetic ingredient.