BACKGROUND: The clinical utility of effective acne vulgaris therapies is hindered by long treatment regimens, adverse events, and poor patient adherence, prompting the search for novel treatment modalities such as photodynamic therapy (PDT). AIM: To evaluate the clinical efficacy and safety of personalized multispectral PDT using a medical light-emitting diode (LED) device for PDT and phototherapy and a combination photosensitizer (0.5% 5-aminolevulinic acid and 0.5% chlorin e6 [5-ALA + Ce6]) in female patients with mild-to-moderate acne vulgaris. METHODS: Ten female patients (aged 17–25 years; mean age, 20.9 ± 2.6 years) with mild-to-moderate acne vulgaris underwent a PDT course comprising 2 to 3 sessions. The intervention utilized a medical LED device for PDT and phototherapy (400 nm [20%], 633 nm [40%], 660 nm [40%], 850 nm [20%]) in conjunction with a 5-ALA + Ce6 combination photosensitizer. Photosensitizer incubation and light exposure lasted 20–40 and 20 min, respectively, with a 1-week interval between sessions. Efficacy was evaluated via the Global Acne Grading System (GAGS), inflammatory lesion counts, and sebumetry/corneometry values. Safety was assessed by the incidence and nature of adverse events. RESULTS: Post-treatment, all patients showed clinical improvement, shifting from moderate to mild acne severity. Significant reductions were observed in mean inflammatory lesion counts (17.30 ± 6.07 to 9.0 ± 4.08; 48% reduction, p 0.001), GAGS scores (18.50 ± 4.25 to 8.70 ± 3.74; 53% reduction, p 0.001), and sebum production (177.30 ± 14.27 to 106.10 ± 16.74 µg/cm2; 40% reduction, p 0.001). Corneometry values increased (35.50 ± 3.63 to 46.20 ± 10.28 AU; 30% increase, p 0.01). Adverse events were mild, transient, and required no intervention. CONCLUSION: Personalized multispectral PDT, utilizing a medical LED device for PDT and phototherapy in conjunction with a 5-ALA + Ce6 combination photosensitizer, demonstrated pronounced clinical efficacy and a favorable safety profile in female patients with mild-to-moderate acne vulgaris. Further studies involving larger sample sizes and a control group are required.