Background: Older adults with low health literacy are at increased risk of nonadherence, accidental drug exposure, and adverse events. Purpose: This study evaluated older adults' knowledge and awareness of medication safety and poison prevention resources using an interactive educational game compared to a less intensive intervention involving individual review of brochures. Methods: Both groups were given pre- and postintervention surveys to assess change in knowledge. Participants were followed up at 30 days to assess knowledge retention and behavior changes. Results: A total of 101 older adults participated in the study. In the game group, the median improvement in the index score pre- and postintervention was 3, moving from 9 (interquartile range [IQR] 6, 9) to 11 (IQR 9, 12). The brochure group median improvement was 1, moving from 7.5 (IQR 6, 8) to 8 (IQR 5, 10). Comparing postintervention to 30-day follow-up, over 50% of respondents retained the correct responses. Discussion: The interactive game significantly improved knowledge regarding use of child-resistant cap, interpreting a drug facts label, medication list documentation, and who to call for advice. Translation to Health Education Practice: This educational intervention has potential to increase awareness of poison prevention resources and medication safety strategies in older adults with low health literacy.