Background and Objectives: The significance of periodontal disease as a public health issue prompts the exploration of effective treatments, including the potential use of tocopherol (Vitamin E) due to its anti-inflammatory and antioxidant properties. Materials and Methods: The PICO statement (Population, Intervention, Comparator, Outcome) was as follows: In patients with periodontal disease, does tocopherol (Vitamin E) supplementation compared to no supplementation or insufficient Vitamin E intake improve clinical outcomes such as gingival inflammation, pocket depth, and clinical attachment levels? This study searched through PubMed, Scopus, and Web of Science up to June 2024 focused on studies involving human subjects with various forms of periodontal disease, analyzing the impact of tocopherol through dietary or supplementary intake. Primary outcomes evaluated included improvements in gingival inflammation, pocket depth, and clinical attachment levels, with data synthesis conducted according to PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. Quality assessment and risk of bias were meticulously performed for the included observational studies and randomized controlled trials. Results: The meta-analysis incorporated 8 studies that were used for data extraction, totaling 12,832 patients, revealing a heterogeneous response to tocopherol supplementation, with a pooled odds ratio for efficacy in reducing periodontal disease severity at about 0.97 (95% CI: 0.96-0.98). Noteworthy findings indicated a statistically significant increase in clinical attachment loss and pocket depth with odds ratios ranging from 1.15 to 9.33 when Vitamin E was insufficient. However, the considerable heterogeneity (I2 = 88.35%) underscores variations in tocopherol's effectiveness across different populations and study designs. Conclusions: While tocopherol supplementation shows a modest benefit in managing periodontal disease, particularly in reducing clinical attachment levels and pocket depth, the variability in outcomes emphasizes the necessity for more research to establish standardized treatment protocols and dosages.