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Environmental sustainability is an increasing challenge in the pharmaceutical field, leading to the search for eco-friendly active ingredients. Among natural ingredients, propolis arises as an excellent alternative, being a complex substance with pharmacological properties. This work aims to explore the potential of propolis as a new pharmaceutical ingredient for the replacement of conventional vulvovaginal antifungals. Propolis extracts were obtained by Ultrasound-Assisted Extraction using different solvents (water, water/ethanol (50:50, v/v), and ethanol). Afterwards, the extracts were characterized regarding total phenolic content (TPC), antioxidant/antiradical activities, radical scavenging capacity, antifungal activity against strains of Candida species, and viability effect on two female genital cell lines. The aqueous extract achieved the best TPC result as well as the highest antioxidant/antiradical activities and ability to capture reactive oxygen species. A total of 38 phenolic compounds were identified and quantified by HPLC, among which ferulic acid, phloridzin and myricetin predominated. Regarding the anti-Candida spp. activity, the aqueous and the hydroalcoholic extracts achieved the best outcomes (with MIC values ranging between 128 and 512 μg/mL). The cell viability assays confirmed that the aqueous extract presented mild selectivity, while the hydroalcoholic and alcoholic extracts showed higher toxicities. These results attest that propolis has a deep potential for vulvovaginal candidiasis management, supporting its economic valorization. [ABSTRACT FROM AUTHOR]