Background and Objectives: Acne vulgaris is a prevalent chronic inflammatory skin condition affecting adolescents and young adults worldwide. Increasing concern regarding antimicrobial resistance has renewed interest in microbiome-modulating therapies, including oral probiotics. This systematic review and meta-analysis evaluated the efficacy and safety of oral probiotic supplementation for acne vulgaris using contemporary random-effects methods. Materials and Methods: Following PRISMA 2020 guidelines, we searched PubMed, Embase, Web of Science, and ClinicalTrials.gov through November 2025 without language restrictions. Eligible studies were double-blind randomized controlled trials (RCTs) comparing oral probiotics with placebo or standard therapy for ≥4 weeks and reporting quantitative acne severity outcomes. Risk of bias was assessed using RoB 2.0. Standardized mean differences (SMDs) were pooled using restricted maximum likelihood (REML) with Hartung-Knapp adjustment. Heterogeneity was summarized using I2, τ2 (95% CI), and 95% prediction intervals. Adverse events were extracted. Results: Three RCTs (n = 231) met eligibility criteria. Pooled analysis suggested a modest reduction in inflammatory lesion counts favoring probiotics (SMD -0.57; 95% CI -0.94 to -0.21), although heterogeneity was substantial (I2 = 72%; τ2 = 0.11). The 95% prediction interval (-1.25 to 0.11) indicated that future studies may plausibly observe no meaningful effect. Sensitivity analyses using the DerSimonian-Laird estimator produced comparable results. All trials reported good short-term tolerability with no serious adverse events. Risk of bias was low in two trials and of some concern in one. Certainty of evidence was rated low to moderate. Conclusions: Oral probiotics may modestly reduce acne severity as a generally safe, antibiotic-sparing adjunct; however, the current evidence base is small and heterogeneous, and the certainty of effect remains low-to-moderate. Larger, standardized RCTs are required before firm clinical recommendations can be made. Registration: PROSPERO CRD420251181388. Funding: This research received no external funding.
Keywords: Acne vulgaris; Bifidobacterium; Lactobacillus; gut–skin axis; meta-analysis; microbiome; oral probiotics; randomized controlled trials; systematic review.