Synergistic Antimicrobial and Antibiofilm Activity Optimization of a Thymus vulgaris–Moringa oleifera–Echinacea purpurea Ternary Ethanolic Extract Blend Against Candida albicans and Streptococcus mutans Using L-Optimal Mixture Design

Antimicrobial resistance and biofilm-associated oral infections require multi-target therapeutic strategies beyond single-extract herbal testing. Using the L-optimal mixture design approach, we optimized a ternary combination of Thymus vulgaris, Moringa oleifera, and Echinacea purpurea ethanolic extracts against Candida albicans and Streptococcus mutans, then characterized the optimized blend’s phytochemistry, antimicrobial and antibiofilm efficacy, time–kill pharmacodynamics, antioxidant capacity, and cytotoxic safety. Through HPLC, apigenin, chlorogenic acid, resorcinol, and ferulic acid were identified as dominant constituents. The optimal blend (Run 14: T. vulgaris 0.331, M. oleifera 0.318, E. purpurea 0.352) achieved a fractional inhibitory concentration index of 0.50 against both organisms, maximum inhibition zones of 3.10 cm (C. albicans) and 4.10 cm (S. mutans), biofilm inhibition of up to 93.2 ± 2.1% for C. albicans and 78.4 ± 2.8% for S. mutans, and confirmed fungicidal and bactericidal activity within 48 and 24 h, respectively. DPPH scavenging ranged from 55.19 to 68.73%, and oral epithelial cells (OEC) viability exceeded 83% at 300 µg/mL. All assays included three independent biological replicates; statistical significance was defined as p < 0.05. These findings identify the T. vulgaris–M. oleifera–E. purpurea blend as a synergistic, multi-target antimicrobial candidate with a favorable preliminary safety profile, supporting further development and evaluation against clinical isolates for oral fungal and bacterial infections.