A major challenge in the health care system is the lack of knowledge about the possible harmful effects of multiple drug treatments in old age. The present study aims to characterize a mouse model of polypharmacy, in order to investigate whether long-term exposure to multiple drugs could lead to adverse outcomes. To this purpose we selected five drugs from the ten most commonly used by older adults in Sweden (metoprolol, paracetamol, aspirin, simvastatin and citalopram). Five-month-old wild type male mice were fed for eight weeks with control or polypharmacy diet. We report for the first time that young adult polypharmacy-treated mice showed a significant decrease in exploration and spatial working memory compared to the control group. This memory impairment was further supported by a significant reduction of synaptic proteins in the hippocampus of treated mice. These novel results suggest that already at young adult age, use of polypharmacy affects explorative behavior and synaptic functions. This study underlines the importance of investigating the potentially negative outcomes from concomitant administration of different drugs, which have been poorly explored until now. The mouse model proposed here has translatable findings and can be applied as a useful tool for future studies on polypharmacy.