Objective: Benign paroxysmal positional vertigo (BPPV), characterized by spinning sensations from vestibular disturbances, significantly impairs patients' quality of life. Given recent links between BPPV, oxidative stress, and inflammation, this study aimed to compare the effects of oral lumbrokinase DLBS1033 and betahistine mesylate on inflammation, quality of life, and dizziness symptoms in BPPV patients.Methods: This randomized controlled double-masked trial was conducted from April to August 2024. We enrolled 44 BPPV patients (18-65 years old), diagnosed via history and Dix-Hallpike maneuver, excluding those with confounding conditions. Quality of life, dizziness severity, and inflammatory biomarkers (TNF-α, IL-1β, VCAM-1) were assessed at baseline, day 7, and day 14. Data were analyzed using SPSS 25.0.Results: Forty-four participants (63.64?male, mean age 48.45±11.02 years) were equally randomized to oral lumbrokinase DLBS1033 (n=22) or betahistine mesylate (n=22) with no dropouts or adverse events. Independent T-tests revealed significant differences between groups' quality of life, dizziness severity, and inflammatory biomarker levels. Oral lumbrokinase DLBS1033 resulted in more rapid improvements in quality of life and inflammation reduction, particularly within the first seven days, confirmed by ANOVA and multiple linear regression.Conclusions: Oral lumbrokinase DLBS1033 demonstrated significant therapeutic advantages over betahistine mesylate for BPPV, shown by reduced pro-inflammatory biomarkers, improved quality of life, and faster dizziness resolution. These findings suggest oral lumbrokinase DLBS1033 is a promising and more effective pharmacotherapeutic option for BPPV. Future research should include direct comparisons with canalith repositioning maneuvers and account for psychological and dietary factors.