Background and Objectives: Burning Mouth Syndrome (BMS) remains a challenging condition to manage, as current treatments show variable efficacy and are often limited by tolerability, particularly in older and medically complex patients. This has prompted interest in topical neuromodulatory strategies targeting peripheral mechanisms while minimizing systemic exposure, with topical pregabalin emerging as a potential option. Materials and Methods: In this prospective longitudinal real-world study, 100 patients with BMS treated at a tertiary referral center received topical pregabalin as an off-label intraoral swish-and-spit solution. Patients were assessed at baseline and after 3 months using validated measures of pain intensity (VAS), qualitative pain perception (SF-MPQ), anxiety (HAM-A), depression (HAM-D), sleep quality (PSQI, ESS), and global clinical severity (CGI-S). Results: After 3 months, median VAS decreased from 8 (IQR 7–9) to 5 (IQR 4–6) and SF-MPQ from 10 (IQR 7–17) to 6.5 (IQR 4–10) (both p < 0.001), with concurrent improvements in anxiety, depressive symptoms, and clinical severity. Overall, 46% of patients achieved ≥30% pain reduction, while 73% and 16% reached ≥20% and ≥50% reductions, respectively. Higher baseline pain predicted greater improvement. No serious adverse events were reported. Conclusions: These findings suggest that topical pregabalin may represent a safe and potentially effective option for BMS, although controlled studies are required to confirm its efficacy.