Polypharmacy is commonly related to poor drug adherence, decreased quality of life and inappropriate prescribing in eldery. Furthermore, this condition also leads to a higher utilization of health services resources, due to the increased risk of adverse drug events, length of stays in hospitals and readmissions rates after discharge. This Systematic Review aimed to synthesize the current evidence that evaluates pharmaceutical services on polymedicated patients, from an economic perspective. Systematic searches were conducted in MEDLINE, SCOPUS and Cochrane Library databases to identify studies that were published until January 2021. Experimental and observational studies were included in this review, using strict inclusion/exclusion criteria and were assessed for quality using the following tools: RoB and ROBINS-I. Two independent reviewers selected the articles and extracted the data. 3,662 articles were retrieved from the databases. After the screening, 18 studies were included: 9 experimental and 9 observational studies. The studies reported that the integration of the pharmacist as a member of the healthcare team provides an optimized use of pharmacotherapy to polymedicated patients and contributes to health promotion, providing reduction of spending on medication, reduction of expenses related to emergency care and hospitalizations and other medical expenses. The ECRs made cost-effectiveness or cost-benefit analysis, and most of the Non Randomized studies had statistically significant cost savings even considering the expenses of pharmaceutical assistance. Experimental studies reported a cost reduction varying between US$ 193 to US$ 4,966 per patient per year. Furthermore, observational studies estimated a cost reduction of varying from US$ 3 to US$ 2,505 per patient per year. The cost savings are related to decrease in emergency visits and hospitalizations, through pharmacist intervention (medication review and pharmacotherapy follow-up). Considering the set of studies included, pharmaceutical care services directed to polymedicated patients may cooperate to save financial resources. Most of the interventions showed positive economic trends and also contributed to improving clinical parameters and quality of life. However, due to the majority of the studies having exploratory or qualitative methodology, it is essential to carry out more robust studies, based on full economic evaluation.