This study aimed to investigate variations in the phytochemical compound contents and antioxidant potential of the ethanol rhizome extracts of Smilax china L., belonging to the Liliaceae family, from different parts of Korea, namely Uiwang (Mt. Gamnamugol), Gyeonggi Province (SC1); Geochang, Gyeongnam Province (SC2); Yeongwol, Gangwon Province (SC3); and Chungju, Chungbuk Province (SC4). The phenolic and flavonoid contents, radical scavenging activity, and proximate composition of the ethanol extracts from the rhizome samples were determined. The total polyphenol content (TPC) of the extracts ranged between 13.6 and 67.5 mg tannic acid equivalent/g. TPC analysis showed that TPC was higher in SC2 than in SC3, SC4, or SC1. Among the rhizome samples, the SC3 rhizomes had the highest total flavonoid content (TFC) (5.2 mg quercetin equivalents/g). Additionally, SC2 showed the highest radical scavenging activity against DPPH and ABTS+ radicals. Chemical characterization using UPLC/UV revealed that the extracts contained compounds such as apiin, kaempferol-3-rutinoside, and chlorogenic acid. Specifically, in SC2, chlorogenic acid was the dominant compound, which supported the levels observed in the UPLC/UV and HPLC/ELSD investigations. Dioscin, another phytochemical, was detected in SC2, SC3, and SC4, indicating the diversity of compounds among the rhizome extracts. Variations in the phytochemical content and antioxidant activity were observed in the extracts from the different regions, underlining the role of geographical variation in the functional characteristics of S. china. The observed differences could have important implications for the medicinal use of S. china extracts in applications such as anti-inflammatory treatments, diabetes management, and potential anticancer therapies. This study underscores the critical need to consider geographical origin when sourcing and utilizing S. china for therapeutic purposes, as it may significantly impact its bioactive profile and efficacy.