This work aims to improve the functionality of Rosmarinus officinalis L. (rosemary) polyphenols by encapsulation in an optimized proliposome formulation. A 2 3 Box-Wilson central composite design (CCD) was employed to determine lone and interaction effects of composition variables on moisture content (X p); water activity (A w); concentration and retention of rosemary polyphenols-rosmarinic acid (ROA), carnosol (CAR), and carnosic acid (CNA); and recovery of spray-dried proliposomes (SDP). Processing conditions which generate proliposomes with optimum physicochemical properties were determined by multi-response analysis (desirability approach). Antioxidant and antifungal activities were evaluated by 1,1-diphenyl-2-picrylhydrazyl (DPPH •) sequestering and minimum inhibitory concentration (MIC)/minimum fungicidal concentration (MFC) assays, respectively. SDP exhibited high polyphenol retention, ranging from 62.0 to 100.0% w/w, showing dependence on composition variables and polyphenol lipophilicity. SDP recovery ranged from 20.1 to 45.8%, with X p and A w of 1.7 ± 0.14-2.5 ± 0.23% w/w and 0.30 ± 0.004-0.47 ± 0.003, respectively, evidencing product with good chemical and microbiological stability. Optimum liposomal composition was determined, namely, lipid concentration (4.26% w/w), lyophilized extract (LE) concentration (4.48% w/w), and drying aid:(lipid+extract) ratio (7.55% w/w) on wet basis. Relative errors between experimental and predicted values for SDP properties showed concurrence for all responses except CAR retention, being 22% lower. SDP showed high antioxidant activity with IC 50 of 9.2 ± 0.2 μg/ mL, superior to results obtained for LE (10.8 μg/mL) and butylated hydroxytoluene (BHT), a synthetic antioxidant (12.5 μg/mL). MIC and MFC against Candida albicans (ATCC1023) were 312.5 μg/mL and 1250 μg/mL, respectively, a moderate antimicrobial activity for phytochemical-based products. SDP is shown as a veritable tool to encapsulate hydrophilic and lipophilic rosemary polyphenols generating a product with optimal physicochemical and biological properties.