Introduction: The increasing complexity of drug regimens over time and the use of multiple medications exposes older patients to a greater risk of receiving inappropriate medications. This study investigated whether Drug Burden Index (DBI) and potentially inappropriate medications (PIMs) were associated with patient-reported health outcomes (PROs) in community-dwelling older adults (aged ≥ 60 years) in Malaysia. Methods: DBI was used to quantify patients’ exposure to anticholinergic and sedative medications in a cross-sectional sample of older individuals from the community pharmacy setting in Malaysia. PIMs (based on Beers criteria), potentially inappropriate prescribing (PIP; based on STOPP criteria) and polypharmacy (use of ≥ 5 concurrent medications) were used to quantify exposure to inappropriate medications. PROs were investigated using the Groningen Frailty Indicator (GFI) for frailty and older people’s quality of life-35 (OPQOL) for quality of life (QOL). The adjusted associations between DBI, medication inappropriateness and PROs were analyzed. Results: More than half of the study participants received ≥ 1 anticholinergic or sedative medications (mean 0.47/participant; range 0.0–2.14). Prevalence of frailty was low (8.90% of patients), with a mean GFI score of 1.67 (range 1–8) and was significantly and positively correlated with DBI (r 0.253; p = 0.003). In multivariate logistic regression, frailty was found to be significantly associated with the odds of receiving DBI-associated medications (odds ratio 1.44; 95% CI 1.02–2.02, p = 0.039). Non-significant associations were found between DBI and QOL domains, except for a significant and positive correlation between the independence domain of OPQOL and PIP. Conclusion: This study indicates a significant relationship between drug burden measured by DBI and frailty measured by GFI. The prescribers managing various medical conditions of older people should consider frailty and other relevant physical health parameters as important health outcomes.