Background and Objectives: Red yeast rice (RYR)-containing food supplements are widely used for mild-to-moderate hypercholesterolemia, but their post-marketing safety remains relevant. This study characterized their safety profile within a structured multicompany nutrivigilance framework. Methods: Spontaneous reports of suspected adverse events (AEs) associated with RYR-containing food supplements were collected between 12 December 2022 and 31 May 2024. Cases were documented using a structured case report form, medically reviewed, and classified for causality according to the World Health Organization-Uppsala Monitoring Centre framework. Exposure was estimated from cumulative manufacturing and sales data. Results: A total of 148 AE reports were collected from 12 European countries. Estimated exposure corresponded to 608,815 exposed subject-periods over 18 months, based on cumulative manufacturing and sales data and recommended daily dosage. Mean age was 65.3 ± 13.3 years; among reports with available age, 58.1% occurred in individuals aged ≥70 years. Gastrointestinal events were most frequent (45.9%), followed by arthromyalgia (16.9%) and hypersensitivity reactions (10.8%). Most events were mild or moderate (97.9%); severe and serious events accounted for 0.7% and 1.4%, respectively. Both serious AEs occurred in individuals aged ≥70 years. The estimated exposure-based reporting rate was 0.02% for all AEs and 0.0003% for serious AEs. Conclusions: Within a structured post-marketing nutrivigilance framework, RYR-containing food supplements showed a low reporting frequency of AEs relative to estimated exposure, with most events being mild or moderate. Future research should strengthen harmonized nutrivigilance systems and integrate product-specific exposure data, formulation characteristics, and post-marketing safety monitoring to support more precise risk assessment.