In Korea, herbal medicines (HMs) are primarily used to treat diseases. Patients with stroke are generally older and take several conventional medicines (CMs) to address other underlying diseases, which is known as polypharmacy. Therefore, there is a growing concern about hepatotoxicity and nephrotoxicity due to drug interactions between HMs and CMs. Therefore, this study retrospectively investigated liver and renal tests in patients with stroke treated with polypharmacy to clarify the safety of simultaneous HM and CM administration. The medical records of 111 patients with stroke treated at a single center and who met the inclusion criteria between March 1, 2017, and March 1, 2022, were reviewed. The HMs and HM prescription frequency, CMs, and liver and kidney test results were recorded. Additionally, the Roussel Uclaf Causality Assessment Method and Kidney Disease Improving Global Outcome scores were documented, which are standard criteria for assessing liver and kidney injury, respectively. The study included 53 men and 58 women (average age: 67.8 years). On average, the patients took 6 types of CMs. No patient showed liver injury during the co-administration of CMs and HMs. Only 1 patient had initial hepatic damage but recovered after taking HMs. Furthermore, 2 patients had liver test abnormalities 2 times the upper limit of normal, possibly from Seogyeong-tang and atorvastatin, with Roussel Uclaf Causality Assessment Method scale scores of 3 and 5, respectively. No patient had a renal injury. HM is safe for patients with stroke taking multiple CMs. However, consulting an HM expert is essential to avoid hepatotoxicity, nephrotoxicity, and other adverse effects. These results highlight the benefits of Korea’s dual medical system.