Polypharmacy is a prevalent issue in older adults, associated with a wide range of adverse health outcomes, amplified in those with frailty. This review aims to synthesize current literature on the prevalence and health outcomes of polypharmacy and hyperpolypharmacy in older adults with frailty. A systematic search was carried out within ten databases till December 2021. Data was extracted using a piloted data extraction form, and methodological quality was assessed using JBI critical appraisal checklists. Meta-analyses were conducted for prevalence, and narrative synthesis was conducted for the health outcomes of polypharmacy and hyperpolypharmacy in older adults with frailty. Heterogeneity was assessed using Chi(2) and I(2) statistics, with sensitivity and subgroup analyses performed to explore sources of heterogeneity. Sixty-six studies were included for this review. The overall pooled prevalence of polypharmacy and hyperpolypharmacy was 59% and 22% respectively. When stratifying the studies by setting, WHO regions, in eighteen frailty assessment instruments, and by its year of publication, subgroup analysis found the highest rates of prevalence in the hospital setting (71%), in the European region (68%), when Reported Edmonton Frail Scale was used (96%), and in studies published in 2015 (86%). Additionally, frail older adults with polypharmacy were less likely to experience an improvement in frailty states, had higher risks of mortality, were more likely to suffer adverse hospital-related outcomes, and required additional assistance compared to those without polypharmacy. Therefore, the high prevalence and poorer health outcomes urges the healthcare providers and health policymakers to develop and implement preventative and restorative measures targeted at the adverse outcomes associated with polypharmacy and hyperpolypharmacy in older adults with frailty.