Ceramide (Cer), a preferred moisturiser, faces challenges related to extraction efficiency and safety issues linked to chemical synthesis. This study explores an optimised methodology for Cer extraction. Rice bran was subjected to co-fermentation using select yeast and lactic acid bacteria (LAB) strains. Comprehensive qualitative characterisation and lipidomic profiling verified compositional changes. Additionally, in vitro and cell-based assays evaluated biological activity. LAB-mediated hydrolysis of starch and cellulose yielded bioavailable carbon sources that enhanced yeast metabolism, facilitating Cer release. Consequently, rice bran extract (RBE) exhibited elevated Cer content and amplified functional efficacy. Notably, Cer-enriched RBE significantly upregulated keratinocyte protein gene expression and augmented antioxidant enzyme activity, while suppressing inflammatory mediators—effects strongly correlated with the Cer_NDS fraction. This work establishes a novel, sustainable approach for high-yield Cer production, outperforming conventional methods in both effectiveness and environmental compatibility, while advancing its translational potential for skincare applications.