Background: Recent advancements have highlighted the potential of cannabis and its phy-tocannabinoids (pCBs) in skin health applications. These compounds, through their interac-tion with the endocannabinoid system (ECS), show promise for skin health products. Their ability to regulate inflammation, oxidative stress, and cellular proliferation makes them bene-ficial in addressing skin issues like inflammation, scarring, healing, acne, and aging, posi-tioning them as valuable tools for innovative skincare solutions. Methods: We investigated the cellular and molecular effects of proprietary pCB-based for-mulations on ECS modulation, inflammation, and skin regeneration. Using human dermal fibroblasts (HDF) and keratinocytes (HaCat), we assessed the formulations in both pre-treatment and treatment scenarios following exposure to stress-inducing agents. Key molecular markers were analyzed to tackle their efficacy in mitigating inflammation and promoting structural integrity and regeneration. Results: Our findings show that these formulations significantly reduce inflammation, pro-mote skin regeneration, and improve structural functions. In vivo studies confirmed that the formulations were well-tolerated and led to noticeable improvements in skin health, including enhanced barrier function. Conclusions: This study demonstrates the safety and efficacy of pCB-based formulations for cosmeceutical applications. By combining molecular analysis with in vivo testing, our research provides new insights into the therapeutic potential of pCBs for managing various skin con-ditions.